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21 pages, 3692 KiB  
Article
Anti-Obesity Effects of Rosa rugosa Thunb. Flower Bud Extracts on Lipid Metabolism Regulation in 3T3-L1 Adipocytes and Sprague Dawley Rats
by Jung Min Kim, Kyoung Kon Kim, Hye Rim Lee, Jae Cheon Im and Tae Woo Kim
Int. J. Mol. Sci. 2025, 26(14), 6963; https://doi.org/10.3390/ijms26146963 - 20 Jul 2025
Viewed by 263
Abstract
In modern society, obesity and its associated complications have emerged as serious public health concerns, primarily stemming from sedentary lifestyles and carbohydrate-rich diets. Due to the severe side effects often associated with pharmacological anti-obesity agents, emerging global efforts focus on preventive strategies, e.g., [...] Read more.
In modern society, obesity and its associated complications have emerged as serious public health concerns, primarily stemming from sedentary lifestyles and carbohydrate-rich diets. Due to the severe side effects often associated with pharmacological anti-obesity agents, emerging global efforts focus on preventive strategies, e.g., dietary modifications and weight gain-suppressing functional foods. In this context, plant-derived metabolites are extensively investigated for their beneficial anti-obesity effects. In this study, we evaluated how Rosa rugosa Thunb. flower bud extract affects fat metabolism in 3T3-L1 preadipocyte cells. The extract significantly inhibited adipocyte differentiation and intracellular triglyceride accumulation in 3T3-L1 cells, enhanced lipolysis, suppressed lipogenesis, and promoted energy metabolism in differentiated adipocytes. In vivo, it reduced body and organ weights and fat mass in high-fat diet-induced obese rats, along with marked adipocyte size and hepatic lipid accumulation reductions. In the epididymal adipose tissue, the extract similarly enhanced lipolytic activity, suppressed lipogenic enzyme expression, and stimulated energy expenditure. Taken together, our results demonstrate the potential of R. rugosa Thunb. flower bud extract in reducing fat accumulation through lipid metabolism modulation both in cellular and animal models. Further studies are warranted to identify the active constituents and evaluate the safety and efficacy of the extract in clinical applications. Full article
(This article belongs to the Special Issue High Fat Diet Metabolism and Diseases)
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20 pages, 4729 KiB  
Article
Cis-Palmitoleic Acid Regulates Lipid Metabolism via Diacylglycerol Metabolic Shunting
by Wenwen Huang, Bei Gao, Longxiang Liu, Qi Song, Mengru Wei, Hongzhen Li, Chunlong Sun, Wang Li, Wen Du and Jinjun Shan
Foods 2025, 14(14), 2504; https://doi.org/10.3390/foods14142504 - 17 Jul 2025
Viewed by 371
Abstract
Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms [...] Read more.
Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article
(This article belongs to the Special Issue Food Bioactive Compounds in Disease Prevention and Health Promotion)
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16 pages, 1438 KiB  
Article
The Effect of Reduced Dietary Protein on Adipose Tissue in Local Krškopolje Pigs
by Klavdija Poklukar, Marjeta Čandek-Potokar, Milka Vrecl, Jana Brankovič, Matjaž Uršič and Martin Škrlep
Int. J. Mol. Sci. 2025, 26(9), 4440; https://doi.org/10.3390/ijms26094440 - 7 May 2025
Viewed by 659
Abstract
The Slovenian autochthonous breed, Krškopolje pig, is known for high fatness and better adaptability to different environmental conditions and feed resources. However, the metabolic processes underlying these adaptations, especially in response to different diets, have not yet been studied. A deeper understanding of [...] Read more.
The Slovenian autochthonous breed, Krškopolje pig, is known for high fatness and better adaptability to different environmental conditions and feed resources. However, the metabolic processes underlying these adaptations, especially in response to different diets, have not yet been studied. A deeper understanding of these mechanisms could provide valuable insights into the breed’s adaptability to different environmental conditions. Therefore, the main objective of this study was to evaluate the effect of a low-protein (LP) diet on adipose tissue in Krškopolje pigs reared in either organic outdoor (n = 2 × 12) or conventional indoor (n = 2 × 14) systems. In the outdoor system, the LP diet had no effect on adipocyte size compared to the control (high-protein) diet, while it increased lipogenic enzyme activities and monounsaturated fatty acid content, and decreased polyunsaturated fatty acid content (p < 0.05). RNA sequencing revealed the upregulation of 28 genes and the downregulation of 37 genes. The upregulated genes were mainly involved in lipid metabolism (ACLY, FASN, ACACA, MOGAT2), oxidative stress, and mitochondrial function. In the indoor system, pigs on the LP diet had smaller adipocytes (p < 0.05), whereas no differences were detected in the lipogenic enzyme activities or fatty acid composition (p > 0.10). RNA sequencing revealed 30 upregulated and 28 downregulated genes. In the indoor system, heat shock proteins (HSP70.2, HSPA6) were upregulated in pigs on the LP diet, while genes involved in the innate immune system (MSR1, TREM2, CSF3R) were downregulated. To conclude, the present study showed that LP diet affected adipose tissue metabolism and gene expression in Krškopolje pigs, with different transcriptomic responses observed in outdoor and indoor rearing conditions. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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29 pages, 4883 KiB  
Article
High-Fat Diet in Perinatal Period Promotes Liver Steatosis and Low Desaturation Capacity of Polyunsaturated Fatty Acids in Dams: A Link with Anxiety-Like Behavior in Rats
by Lorena Mercado-López, Yasna Muñoz, Camila Farias, María Paz Beyer, Robinson Carrasco-Gutiérrez, Angie Vanessa Caicedo-Paz, Alexies Dagnino-Subiabre, Alejandra Espinosa and Rodrigo Valenzuela
Nutrients 2025, 17(7), 1180; https://doi.org/10.3390/nu17071180 - 28 Mar 2025
Viewed by 862
Abstract
Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control [...] Read more.
Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control diet, CD (n = 6), or HFD (n = 6) for 12 weeks, encompassing mating, gestation, and lactation periods (18 weeks). Anxiety-like behavior, maternal behavior, depression-like behavior, and social play were studied. Post mortem, the liver function, hepatic steatosis, and fatty acid composition (erythrocytes, liver, adipose tissue) were evaluated. In regard to desaturase enzymes (Δ-6D and Δ-5D), liver activity, protein mass, and gene expression (RT-PCR) were analyzed. Additionally, gene expression of PPAR-α, ACOX, CPT1-α, SREBP-1c, ACC, and FAS was assessed. Statistical analysis was performed using Student’s t-test, mean ± SD (p < 0.05). Results: The HFD significantly increased maternal weight and anxiety-like behavior while reducing social interactions exclusively in male offspring (p < 0.05). It also led to a significant decrease in the synthesis and content of n-3 PUFAs in the analyzed tissues, induced hepatic steatosis, and upregulated the expression of pro-lipogenic genes in the maternal liver. Conclusions: These findings suggest that long-term HFD consumption alters tissue fatty acid composition, disrupts metabolic homeostasis, and contributes to behavioral changes, increasing anxiety-like behaviors in pregnant dams and reducing social interactions in male offspring. Overall, this study provides further insight into the detrimental effects of HFD consumption during the perinatal period. Full article
(This article belongs to the Special Issue Dietary Fatty Acids and Metabolic Health)
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14 pages, 1613 KiB  
Article
Application of Branched-Chain Amino Acids Mitigates Mitochondrial Damage to Spotted Seabass (Lateolabrax maculatus) Hepatocytes Cultured in High-Glucose and High-Fat Media
by Huijuan Ren, Yixiong Ke, Xueshan Li, Lin Wang, Kai Song, Francisco A. Guardiola, Chunxiao Zhang, Kangle Lu and Samad Rahimnejad
Animals 2025, 15(4), 560; https://doi.org/10.3390/ani15040560 - 14 Feb 2025
Viewed by 898
Abstract
This study explored the metabolic effects of branched-chain amino acids (BCAAs) on the hepatocytes of spotted seabass (Lateolabrax maculatus) under high-glucose (HG) or high-fat (HF) conditions. Hepatocytes were cultured under five different conditions: control, high glucose (HG), HG + BCAAs (Leu [...] Read more.
This study explored the metabolic effects of branched-chain amino acids (BCAAs) on the hepatocytes of spotted seabass (Lateolabrax maculatus) under high-glucose (HG) or high-fat (HF) conditions. Hepatocytes were cultured under five different conditions: control, high glucose (HG), HG + BCAAs (Leu 0.8 mM, Ile 0.4 mM, Val 0.8 mM), high fat (HF), and HF + BCAAs (Leu 0.8 mM, Ile 0.8 mM, Val 0.8 mM). After 72 h of culture, cells and cell supernatants were collected to measure relevant indicators. The results revealed that BCAAs supplementation significantly reduced glycogen and lipid accumulation in hepatocytes exposed to HG or HF conditions (p < 0.05). Additionally, alanine aminotransferase and aspartate aminotransferase activities in the supernatant were significantly decreased, indicating that BCAAs supplementation alleviated hepatocyte damage induced by these conditions. Furthermore, BCAAs addition markedly enhanced antioxidant defense by increasing superoxide dismutase and catalase activities, improving total antioxidant capacity, and reducing malondialdehyde levels. Metabolic enzyme activity analysis revealed that BCAAs significantly increased the activities of citrate synthase (CS), alpha-ketoglutarate dehydrogenase complex (α-KGDHC), succinate dehydrogenase (SDH), phosphoenolpyruvate carboxykinase (PEPCK), and liver pyruvate kinase (LPS), while significantly decreasing fatty acid synthase (FAS) activity. Gene expression analysis further demonstrated that BCAAs supplementation downregulated the expression of lipogenic genes (fas and srebp-1c) and upregulated the expression of lipolytic genes (ppaα and atgl) and glucose metabolism-related genes (g6pd, hk, pfk, pk, fbp, and g6pase). Under HG or HF conditions, hepatocytes exhibited decreased adenosine triphosphate (ATP) content, increased reactive oxygen species (ROS) levels, and reduced mitochondrial membrane potential. These adverse effects were mitigated by BCAAs supplementation. In conclusion, BCAAs supplementation alleviated hepatocyte damage caused by HG or HF conditions, enhanced antioxidant defenses, and protected mitochondrial activity and function by promoting glucose and lipid metabolism. Full article
(This article belongs to the Section Aquatic Animals)
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21 pages, 1410 KiB  
Review
The Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review
by Antonio Paoli
Nutrients 2025, 17(4), 663; https://doi.org/10.3390/nu17040663 - 13 Feb 2025
Cited by 3 | Viewed by 7360
Abstract
De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription [...] Read more.
De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription factors like SREBP-1c, adipose DNL is more modest and less sensitive to dietary overfeeding. Dysregulated DNL contributes to metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle interventions, such as physical exercise, ketogenic diets, and time-restricted eating (TRE) offer promising strategies to regulate DNL and improve metabolic health. Physical exercise enhances glucose uptake in muscles, reduces insulin levels, and promotes lipid oxidation, thereby suppressing hepatic DNL. Endurance and resistance training also improve mitochondrial function, further mitigating hepatic triglyceride accumulation. Ketogenic diets shift energy metabolism toward fatty acid oxidation and ketogenesis, lower insulin, and directly downregulate lipogenic enzyme activity in the liver. TRE aligns feeding with circadian rhythms by optimizing AMP-activated protein kinase (AMPK) activation during fasting periods, which suppresses DNL and enhances lipid metabolism. The combined effects of these interventions demonstrate significant potential for improving lipid profiles, reducing hepatic triglycerides, and preventing lipotoxicity. By addressing the distinct roles of the liver and adipose DNL, these strategies target systemic and localized lipid metabolism dysregulation. Although further research is needed to fully understand their long-term impact, these findings highlight the transformative potential of integrating these approaches into clinical practice to manage metabolic disorders and their associated complications. Full article
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14 pages, 3714 KiB  
Article
Experimental Validation of Antiobesogenic and Osteoprotective Efficacy of Ginsenoside CK via Targeting Lipid and Atherosclerosis Pathways
by Md. Niaj Morshed, Reshmi Akter, Imran Mahmud, Ah-Yeong Gwon, Jin Woo Jeang, Yeong-Geun Lee, Dae Won Park, Deok Chun Yang, Yeon Ju Kim and Se-Chan Kang
Life 2025, 15(1), 41; https://doi.org/10.3390/life15010041 - 31 Dec 2024
Viewed by 1151
Abstract
The present study explored the possible antiobesogenic and osteoprotective properties of the gut metabolite ginsenoside CK to clarify its influence on lipid and atherosclerosis pathways, thereby validating previously published hypotheses. These hypotheses were validated by harvesting and cultivating 3T3-L1 and MC3T3-E1 in adipogenic [...] Read more.
The present study explored the possible antiobesogenic and osteoprotective properties of the gut metabolite ginsenoside CK to clarify its influence on lipid and atherosclerosis pathways, thereby validating previously published hypotheses. These hypotheses were validated by harvesting and cultivating 3T3-L1 and MC3T3-E1 in adipogenic and osteogenic media with varying concentrations of CK. We assessed the differentiation of adipocytes and osteoblasts in these cell lines by applying the most effective doses of CK that we initially selected. Using 3T3-L1 adipocytes in vitro assessments, CK could effectively decrease intracellular lipid accumulation, inhibit α-glucosidase enzyme, increase 2-NBDG glucose uptake, reduce inflammation-associated cytokines (TNFα, and IL-6), adipogenic regulatory genes (PPARγ, FAS, C/EBPα), lipogenic gene LPL, and increase the expression of thermogenic gene UCP1. Additionally, CK treatment induced osteoblast development in MC3T3-E1 cells as shown by increased mineralization and calcium distribution, collagen content, alkaline phosphatase activity, and decreased inflammatory cytokines TNFα, and IL-6 and increased the regulated expressions of osteogenic genes including Runx2, ALP, BGLAP, OCN, and Col1a1. Significantly, as a major inhibitory regulator, the TP53 gene was down-regulated in both 3T3-L1 and MC3T3E1 cells after the treatment of CK. These encouraging results demonstrate the possible use of CK as an innovative treatment for controlling obesity and osteoporosis, targeting the underlying mechanisms of obesogenic and bone loss. Further studies are necessary to explore the clinical implications of these results and the potential of CK in future treatment strategies. This research highlights the promise of CK in addressing significant health issues. Full article
(This article belongs to the Section Pharmaceutical Science)
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19 pages, 321 KiB  
Article
Growth Performance, Carcass Quality, and Lipid Metabolism in Krškopolje Pigs and Modern Hybrid Pigs: Comparison of Genotypes and Evaluation of Dietary Protein Reduction
by Martin Škrlep, Klavdija Poklukar, Milka Vrecl, Jana Brankovič and Marjeta Čandek-Potokar
Animals 2024, 14(22), 3331; https://doi.org/10.3390/ani14223331 - 19 Nov 2024
Cited by 2 | Viewed by 1272
Abstract
This study compared the performance, meat quality and adipose tissue characteristics of Krškopolje pigs and modern hybrid pigs under identical rearing conditions, besides examining the effects of dietary protein reduction in both genotypes. A total of 29 pigs (14 Krškopolje and 15 hybrids) [...] Read more.
This study compared the performance, meat quality and adipose tissue characteristics of Krškopolje pigs and modern hybrid pigs under identical rearing conditions, besides examining the effects of dietary protein reduction in both genotypes. A total of 29 pigs (14 Krškopolje and 15 hybrids) were assigned to litter into two dietary groups (high and low protein). The low-protein diet for hybrid pigs corresponded to the high-protein diet for Krškopolje pigs. All diets were iso-energetic. Dietary protein reduction decreased growth rate and muscle development in modern hybrids but had no significant impact on performance, quality or metabolic traits in Krškopolje pigs. Genotype differences revealed that Krškopolje pigs had lower growth rates, less lean and more fat deposition, as reflected in thicker subcutaneous and higher intramuscular fat compared to modern hybrids. Krškopolje pigs also exhibited higher myoglobin concentration and fatty acid saturation. Lipogenic enzyme activity and histo-morphological traits behaved in a tissue-specific manner but still indicated a greater lipogenic potential in Krškopolje pigs. This study provides valuable insights into breed-specific responses to dietary changes and highlights the unique characteristics of Krškopolje pigs. Full article
(This article belongs to the Special Issue Impact of Genetics and Feeding on Growth Performance of Pigs)
13 pages, 4562 KiB  
Article
Metabolomics Reveals the Mechanism by Which Sodium Butyrate Promotes the Liver Pentose Phosphate Pathway and Fatty Acid Synthesis in Lactating Goats
by Lin Li, Xi Chen, Shuping Yan and Yuanshu Zhang
Animals 2024, 14(22), 3249; https://doi.org/10.3390/ani14223249 - 13 Nov 2024
Cited by 1 | Viewed by 1310
Abstract
This study aimed to explore the effects of sodium butyrate on liver metabolism in goats subjected to a high-concentrate diet. We randomly assigned twelve Saanen-lactating goats into two groups, one of which received a high-concentrate diet (concentrate: forage = 60:40, control group), while [...] Read more.
This study aimed to explore the effects of sodium butyrate on liver metabolism in goats subjected to a high-concentrate diet. We randomly assigned twelve Saanen-lactating goats into two groups, one of which received a high-concentrate diet (concentrate: forage = 60:40, control group), while the other received the same basal diet supplemented with sodium butyrate (SB) (10 g/kg basal diet, SB group). Compared with the control diet, the SB diet considerably increased the milk fat percentage and content (p < 0.05), with an increase of 0.67% in the milk fat content of the SB group. By employing a global metabolomics approach based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS), we identified 6748 ions in ESI+ mode and 3573 ions in ESI− mode after liver isolation from both groups. A total of twenty-three metabolites, including phospholipids, fatty acids, and ribose phosphate, were found to be dysregulated according to a search against the human metabolome database (HMDB). Pathway analysis revealed activation of the pentose phosphate pathway, glycerophospholipid metabolism, and unsaturated fatty acid synthesis. The SB diet also modulated the expression of key lipogenic enzymes, such as acetyl-CoA carboxylase (ACC) and stearoyl-CoA desaturase (SCD-1), which are downstream targets of the transcription factor sterol regulatory element-binding proteins-1c (SREBP-1c), inducing a significant upregulation (p < 0.05). Furthermore, 6-phosphogluconate dehydrogenase (6PGDH) levels in the liver were elevated after the lactating goats were fed the SB diet (p < 0.05). Our study reveals that the SB diet may offer substantial benefits in enhancing the milk quality of subacute ruminal acidosis (SARA) goats. This is accomplished by augmenting the activity of the liver pentose phosphate pathway and the process of de novo fatty acid synthesis in lactating goats. Full article
(This article belongs to the Section Small Ruminants)
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12 pages, 1927 KiB  
Article
Two Regions with Different Expression of Lipogenic Enzymes in Rats’ Posterior Subcutaneous Fat Depot
by Jacek Turyn, Ewa Stelmanska and Sylwia Szrok-Jurga
Int. J. Mol. Sci. 2024, 25(21), 11546; https://doi.org/10.3390/ijms252111546 - 27 Oct 2024
Cited by 2 | Viewed by 1554
Abstract
Lipid metabolism in various adipose tissue depots can differ vastly. This also applies to lipogenesis, the process of synthesizing fatty acids from acetyl-CoA. This study compared the expression of some lipogenic enzymes: fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and malic enzyme 1 [...] Read more.
Lipid metabolism in various adipose tissue depots can differ vastly. This also applies to lipogenesis, the process of synthesizing fatty acids from acetyl-CoA. This study compared the expression of some lipogenic enzymes: fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and malic enzyme 1 (ME1) in different regions of the posterior subcutaneous adipose tissue in rats. Methods and Results: Posterior subcutaneous adipose tissue collected from twelve-month-old Wistar rats was divided into six parts (A–F). The expression of genes encoding lipogenic enzymes was assessed by measuring their activity and mRNA levels using real-time PCR. In the gluteal region of the fat pad, there were much higher levels of activity and mRNA for these lipogenic enzymes compared to the dorsolumbar region. The mRNA level of FASN increased by more than twentyfold, whereas the level of ME1 and ACLY increased eight- and fivefold respectively. This phenomenon was observed in both old and young animals. Furthermore, the lack of uncoupling protein one (Ucp1) expression suggests that neither the presence of brown adipocytes in the gluteal part nor the transformation of white adipocytes into beige contributed to the observed differences. Conclusion: These results indicate that the gluteal white adipose tissue appears to be a unique and separate subcutaneous fat depot. Full article
(This article belongs to the Special Issue CoA in Health and Disease 3.0)
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14 pages, 2315 KiB  
Article
No Difference in Liver Damage Induced by Isocaloric Fructose or Glucose in Mice with a High-Fat Diet
by Wei-Fan Hsu, Ming-Hsien Lee, Chong-Kuei Lii and Cheng-Yuan Peng
Nutrients 2024, 16(20), 3571; https://doi.org/10.3390/nu16203571 - 21 Oct 2024
Cited by 1 | Viewed by 2179
Abstract
Background/Objectives: The diverse effects of fructose and glucose on the progression of metabolic dysfunction-associated steatotic liver disease remain uncertain. This study investigated the effects, in animal models, of high-fat diets (HFDs) supplemented with either glucose or fructose. Methods: Six-week-old, male C57BL/6J [...] Read more.
Background/Objectives: The diverse effects of fructose and glucose on the progression of metabolic dysfunction-associated steatotic liver disease remain uncertain. This study investigated the effects, in animal models, of high-fat diets (HFDs) supplemented with either glucose or fructose. Methods: Six-week-old, male C57BL/6J mice were randomly allocated to four groups: normal diet (ND), HFD, HFD supplemented with fructose (30% w/v, HFD + Fru), and HFD supplemented with glucose (initially 30%, HFD + Glu). After 24 weeks, liver and plasma samples were gathered for analysis. In addition, 39 patients with obesity undergoing bariatric surgery with wedge liver biopsy were enrolled in the clinical study. Results: The HFD + Glu group consumed more water than did the HFD and HFD + Fru groups. Thus, we reduced the glucose concentration from 30% at baseline to 15% at week 2 and 10% starting from week 6. The HFD + Fru and HFD + Glu groups had a similar average caloric intake (p = 0.463). The HFD increased hepatic steatosis, plasma lipid levels, lipogenic enzymes, steatosis-related oxidative stress, hepatic inflammation, and early-stage liver fibrosis. Supplementation with fructose or glucose exacerbated liver damage, but no significant differences were identified between the two. The expression patterns of hepatic ceramides in HFD-fed mice (with or without supplemental fructose or glucose) were similar to those observed in patients with obesity and severe hepatic steatosis or metabolic dysfunction–associated steatohepatitis. Conclusions: Fructose and glucose similarly exacerbated liver damage when added to an HFD. Ceramides may be involved in the progression of hepatic lipotoxicity. Full article
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17 pages, 11847 KiB  
Article
Hepatic Steatosis Can Be Partly Generated by the Gut Microbiota–Mitochondria Axis via 2-Oleoyl Glycerol and Reversed by a Combination of Soy Protein, Chia Oil, Curcumin and Nopal
by Mónica Sánchez-Tapia, Sandra Tobón-Cornejo, Lilia G. Noriega, Natalia Vázquez-Manjarrez, Diana Coutiño-Hernández, Omar Granados-Portillo, Berenice M. Román-Calleja, Astrid Ruíz-Margáin, Ricardo U. Macías-Rodríguez, Armando R. Tovar and Nimbe Torres
Nutrients 2024, 16(16), 2594; https://doi.org/10.3390/nu16162594 - 6 Aug 2024
Cited by 5 | Viewed by 2711
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat–sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed the HFS diet for 7 months. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance, lipogenic and antioxidant enzymes, hepatic 2-OG measurement, and mitochondrial function of the rats were evaluated. Also, the effect of the consumption of functional food with an HFS diet was assessed. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of the HFS diet in Wistar rats caused oxidative stress, hepatic steatosis, and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. The addition of functional foods to the diet modified the gut microbiota, reducing Blautia producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. To use 2-OG as a biomarker, this metabolite was measured in healthy subjects or with MASLD, and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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54 pages, 3588 KiB  
Review
The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity
by Leah E. Jamerson and Patrick C. Bradshaw
Antioxidants 2024, 13(7), 820; https://doi.org/10.3390/antiox13070820 - 8 Jul 2024
Cited by 3 | Viewed by 4177
Abstract
Dietary restriction (DR) protocols frequently employ intermittent fasting. Following a period of fasting, meal consumption increases lipogenic gene expression, including that of NADPH-generating enzymes that fuel lipogenesis in white adipose tissue (WAT) through the induction of transcriptional regulators SREBP-1c and CHREBP. SREBP-1c knockout [...] Read more.
Dietary restriction (DR) protocols frequently employ intermittent fasting. Following a period of fasting, meal consumption increases lipogenic gene expression, including that of NADPH-generating enzymes that fuel lipogenesis in white adipose tissue (WAT) through the induction of transcriptional regulators SREBP-1c and CHREBP. SREBP-1c knockout mice, unlike controls, did not show an extended lifespan on the DR diet. WAT cytoplasmic NADPH is generated by both malic enzyme 1 (ME1) and the pentose phosphate pathway (PPP), while liver cytoplasmic NADPH is primarily synthesized by folate cycle enzymes provided one-carbon units through serine catabolism. During the daily fasting period of the DR diet, fatty acids are released from WAT and are transported to peripheral tissues, where they are used for beta-oxidation and for phospholipid and lipid droplet synthesis, where monounsaturated fatty acids (MUFAs) may activate Nrf1 and inhibit ferroptosis to promote longevity. Decreased WAT NADPH from PPP gene knockout stimulated the browning of WAT and protected from a high-fat diet, while high levels of NADPH-generating enzymes in WAT and macrophages are linked to obesity. But oscillations in WAT [NADPH]/[NADP+] from feeding and fasting cycles may play an important role in maintaining metabolic plasticity to drive longevity. Studies measuring the WAT malate/pyruvate as a proxy for the cytoplasmic [NADPH]/[NADP+], as well as studies using fluorescent biosensors expressed in the WAT of animal models to monitor the changes in cytoplasmic [NADPH]/[NADP+], are needed during ad libitum and DR diets to determine the changes that are associated with longevity. Full article
(This article belongs to the Special Issue Oxidative Stress in Adipose Tissue)
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21 pages, 4302 KiB  
Article
Bioactive Peptides from Meretrix lusoria Enzymatic Hydrolysate as a Potential Treatment for Obesity in db/db Mice
by Ramakrishna Chilakala, Hyeon Jeong Moon, Min Seouk Jung, Jong Won Han, Kang Ho Ko, Dong Sung Lee and Sun Hee Cheong
Nutrients 2024, 16(12), 1913; https://doi.org/10.3390/nu16121913 - 17 Jun 2024
Cited by 4 | Viewed by 1765
Abstract
Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, [...] Read more.
Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals. Full article
(This article belongs to the Section Nutrition and Obesity)
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Article
Fatty Acids and Their Lipogenic Enzymes in Anorexia Nervosa Clinical Subtypes
by Nhien Nguyen, D. Blake Woodside, Eileen Lam, Oswald Quehenberger, J. Bruce German and Pei-an Betty Shih
Int. J. Mol. Sci. 2024, 25(10), 5516; https://doi.org/10.3390/ijms25105516 - 18 May 2024
Cited by 3 | Viewed by 1436
Abstract
Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs [...] Read more.
Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN. Full article
(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)
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