Search Results (513)

Background: High-carbohydrate high-fat (HCHF) diets have been associated with oxidative stress, impaired bone remodelling, and deterioration of skeletal integrity. Kelulut honey (KH), a stingless bee honey rich in antioxidant compounds, has demonstrated protective effects against bone loss; however, its effects on bone density, biomechanical properties, antioxidant status, and bone-related molecular markers remain incompletely understood. (2) Methods: Male Wistar rats were assigned to sham, negative control (NC), or KH-treated groups (200, 400, and 600 mg/kg). The NC and KH groups received an HCHF diet for 24 weeks, with KH administered during the final 12 weeks. Bone microarchitecture was evaluated using micro-computed tomography, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and biomechanical properties by three-point bending. Antioxidant enzyme activities, serum bone turnover markers, and bone-related gene expression were also assessed. (3) Results: HCHF feeding reduced BMD, load, stress, Young’s modulus, gluthatione peroxidase (GPx) activity, and superoxide dismutase (SOD) activity while increasing strain, displacement, serum C-terminal telopeptide of type 1 collagen (CTX-1) and receptor activator of nuclear factor-κB (RANK) levels, and runt-related transcription factor 2 (Runx2) expression. KH supplementation improved bone health by dose-dependently enhancing antioxidant defences, significantly increasing GPx and SOD activities, while catalase (CAT) activity was elevated at 600 mg/kg. The 400 mg/kg dose improved trabecular microarchitecture by increasing trabecular number, connectivity density and cortical area/total tissue area. KH also improved biomechanical properties, increasing load, stress, stiffness, and Young’s modulus while reducing displacement. Furthermore, KH attenuated HCHF-induced increases in Runx2 mRNA and RUNX2 protein and reduced osterix (Sp7), integrin Subunit Alpha 5 (Itga5), and calcitonin receptor (Calcr) mRNA expression. However, serum CTX-1 remained elevated in all KH-treated groups. (4) Conclusions: Overall, the findings suggest that KH may have potential as a natural intervention for mitigating diet-associated skeletal alterations, although further studies are required to clarify the underlying mechanisms. Full article

Obesity-associated metabolic disorders are characterized by impaired glucose and lipid metabolism, insulin resistance, and adipose tissue dysfunction. Interferon regulatory factor 1 (IRF1) is a transcription factor primarily involved in immune regulation; however, its role in adipocyte metabolic regulation remains incompletely understood. In this study, adipocyte-specific Irf1 knockout (Irf1 AKO) mice were generated using the Cre/loxP system and subjected to either a regular chow diet or a high-fat diet (HFD). Metabolic phenotyping, insulin signaling analysis, mitochondrial homeostasis-related assessment, and in vitro adipocyte experiments were performed. Adipocyte-specific IRF1 deficiency improved insulin-stimulated AKT phosphorylation in white adipose tissues and enhanced glucose tolerance and insulin sensitivity under HFD conditions. These metabolic improvements were accompanied by reduced oxygen consumption, energy expenditure, heat production, β3-adrenergic-induced lipolytic response, and cold tolerance. At the molecular level, IRF1 deficiency was associated with reduced TOMM20 expression, decreased mtDNA content, downregulation of oxidative phosphorylation-related genes, and reduced ATP levels in adipose tissues, suggesting altered mitochondrial homeostasis. In 3T3-L1 adipocytes, IRF1 knockdown increased insulin-stimulated AKT activation, glucose uptake, and lipid accumulation, whereas IRF1 overexpression showed opposite trends. Collectively, these findings suggest that adipocyte IRF1 is associated with insulin signaling, lipid metabolic remodeling, and mitochondrial homeostasis, and highlight a potential dissociation between improved insulin responsiveness and reduced energy expenditure in diet-induced obesity. Full article

Prebiotic-mediated gut microbiota modulation is a promising approach for obesity management. Red onions have been identified as a potential source of inulin and inulin neoseries oligosaccharides. This study evaluated the in vivo effects of short-chain inulin and inulin neoseries oligosaccharides (SCIINOs) on the fecal microbiota of obese rats and assessed their potential role in obesity attenuation. Male Wistar rats were fed a high-fat diet (HFD) for 16 weeks to induce obesity, while control rats received a normal diet (ND). From weeks 16 to 24, HFD-fed obese rats were randomly assigned to four groups: SCIINOs at 0.5 g/day, SCIINOs at 1 g/day, atorvastatin (10 mg/kg/day), or no intervention. Obesity status was confirmed by increased body weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and higher food and energy intakes. SCIINOs were enzymatically hydrolyzed and purified by yeast treatment and chromatographic methods. After 8 weeks of SCIINO administration (1 g/day), the fecal microbiota was markedly enriched in Bifidobacterium and Allobaculum, whereas Blautia abundance significantly decreased. SCIINOs also increased taxa negatively associated with obesity-related parameters, including Dubosiella, Rothia, Parabacteroides, Eubacterium, and Coriobacteriaceae UCG-002, which correlated with reductions in body weight, triglycerides, TC, LDL-C, and fasting blood glucose, along with increased high-density lipoprotein cholesterol (HDL-C). In parallel, SCIINOs increased fecal acetate and butyrate levels, which was consistent with the enrichment of Bifidobacterium and butyrate-producing bacteria. Overall, SCIINOs derived from red onions show promise as a prebiotic candidate for obesity attenuation through selective microbiota modulation and enhanced short-chain fatty acid production. Full article

Obesity is a chronic metabolic disorder closely associated with dyslipidemia, insulin resistance, low-grade inflammation, and gut microbiota dysbiosis. Mulberry leaves are rich in bioactive proteins, but whether mulberry leaf albumin-type protein can improve diet-induced obesity remains unclear. In this study, ultrafiltered mulberry leaf albumin-type protein (UMP) was prepared and its anti-obesity effects were evaluated in high-fat diet (HFD)-fed C57BL/6J mice. UMP contained 87.12 ± 0.52 g/100 g protein, 2.52 ± 0.00 g/100 g polyphenols, and 8.21 ± 1.49 g/100 g polysaccharides, with two major albumin-type protein bands of approximately 14 and 52 kDa. Structural analysis showed that UMP was mainly composed of β-turns and α-helices. In HFD-fed mice, daily administration of UMP for 16 weeks reduced body weight gain by 3.85 g and 5.63 g in the low- and high-dose groups, respectively, without affecting food intake. Biochemical assays, glucose and insulin tolerance tests, and histological analysis showed that UMP improved insulin responsiveness, alleviated serum dyslipidemia, reduced hepatic lipid accumulation, and decreased circulating alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide levels. Histological analysis and nuclear magnetic resonance-based short-chain fatty acid quantification further showed that UMP protected colonic morphology and increased colonic short-chain fatty acid levels. Gut microbiota analysis showed that UMP restored microbial diversity, reduced the Firmicutes/Bacteroidota ratio, and enriched potentially beneficial genera, including Ileibacterium and norank_f_Muribaculaceae. Fecal biochemical assays suggested that UMP promoted fecal free fatty acid excretion and partially improved bile acid-related metabolic alterations. Untargeted serum metabolomics revealed that UMP reshaped metabolic pathways related to lipid turnover, bile acid signaling, glucose utilization, and glucuronidation. Correlation analysis linked UMP-enriched bacterial taxa with key metabolites involved in fatty acid and energy metabolism. Together, these findings indicate that UMP attenuates HFD-induced obesity through coordinated regulation of gut microbiota, intestinal metabolites, and systemic metabolic homeostasis. UMP may therefore represent a promising functional dietary protein for the prevention of obesity-related metabolic disorders. Full article

The global rise in obesity and associated metabolic disorders has fueled the demand for safe, multi-target therapeutics derived from natural sources. In this study, an artificial neural network combined with a genetic algorithm (ANN-GA), was employed to optimize the ultrasound-assisted extraction of loquat leaf extract (LLE). The optimal parameters—0.6% Tween 80, 328 W ultrasonic power, and 49 °C—enhanced extraction efficiency while minimizing energy consumption and surfactant use. In vitro, LLE exhibited potent dose-dependent inhibition of α-glucosidase (IC₅₀ = 3.75 μg/mL, 21.6-fold stronger than acarbose) and pancreatic lipase (IC₅₀ = 78.3 μg/mL), indicating strong inhibitory activity against these digestive enzymes. In high-fat diet-induced obese mice, LLE supplementation dose-dependently reduced body weight gain, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose while elevating high-density lipoprotein cholesterol (HDL-C). In addition, LLE ameliorated liver injury (decreased ALT/AST) and oxidative stress (lowered MDA, increased SOD). These findings highlight LLE as a promising multi-target natural product for managing obesity and related metabolic disorders. Full article

Examining the relationship between an animal’s diet and physiology is crucial to understanding their responses to environmental change. Dietary-induced physiological variation can influence key life history processes, including growth and reproduction, ultimately affecting individual fitness. Reported here are the plasma biochemical parameters related to energy storage, use and nutritional condition in juvenile white sharks (Carcharodon carcharias) in Eastern Australia. Specifically, we used plasma metabolites (triglyceride, cholesterol and β-hydroxybutyrate), thyroid hormone thyroxine and fatty acid profiles from 50 juvenile white sharks (152–340 cm total length) captured on SMART drumlines in Eastern Australia to examine blood biochemistry and nutritional ecology. Concentrations of triglycerides and β-hydroxybutyrate indicated high energy expenditure likely associated with the broad-scale migration of white sharks along the Australian coast, highlighting the importance of β-hydroxybutyrate as an energy source. Seasonal variation in the triglyceride/cholesterol and ω3/ω6 fatty acid ratio, in conjunction with lower docosahexaenoic acid, suggests that lower-quality prey is consumed during winter months, thereby influencing the nutritional condition of these sharks. Additionally, the positive correlation between thyroxine concentrations and water temperature suggests reduced metabolic activity during cooler months. Such fluxes in food quality and nutritional condition may affect juvenile white sharks’ growth and development rate and future reproductive success. Full article

Gut lactic acid bacteria are emerging as potential targets for modulating host purine metabolism and alleviating hyperuricemia-related disorders. This study aimed to isolate purine-degrading lactic acid bacterial strains from porcine intestine and systematically evaluate their probiotic potential through both in vitro and in vivo approaches. A strain designated Pedio6-1 was isolated and identified as Pediococcus acidilactici based on 16S rRNA sequencing. In vitro assays demonstrated that P. acidilactici Pedio6-1 exhibited nearly complete adenine clearance (approaching 100%) and a total purine clearance rate of 30.73%, along with strong tolerance to acidic conditions, bile salts, and gastrointestinal enzymes. To further assess its in vivo efficacy, a high-fat diet-induced obese mouse model was employed. After 8 weeks of intervention, Pedio6-1 supplementation significantly reduced the final body weight and liver index, and markedly decreased hepatic guanine levels (p < 0.05), with a trend toward lower total purine content compared to the obese control group. Mechanistically, Pedio6-1 treatment significantly downregulated the hepatic mRNA expression of pro-inflammatory cytokines IL-1β and TLR4 (p < 0.05). Serum untargeted metabolomics revealed that Pedio6-1 treatment shifted the metabolic profile toward that of normal diet-fed mice, with differential pathways predominantly enriched in porphyrin metabolism and amino acid biosynthesis and metabolism. Notably, key metabolites with antioxidant and metabolic regulatory functions, including bilirubin, biliverdin, glutathione, citrate, L-cystathionine, and 4-pyridoxic acid, were significantly elevated following treatment, while N-acetylornithine and methylmalonate ester were decreased, indicating coordinated remodeling of oxidative stress defense, vitamin B6 homeostasis, and energy metabolism. Collectively, these findings indicate that Pedio6-1 not only possesses direct purine-degrading activity in vitro, but also ameliorates purine metabolic disturbances, inflammation, and oxidative stress in obese mice, likely through the modulation of porphyrin and amino acid metabolic pathways, highlighting its promise as a functional probiotic candidate for managing obesity-associated purine metabolic disorders. Full article

Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all cancers. Among HNCs, neck squamous cell carcinoma (HNSCC) is predicted to become the most common form of human cancer. Some sources include oesophagus (ESCC) in this group due to their similar histology, being described as upper aerodigestive tract cancers (UADT). Unfortunately, 60–70% of cases are diagnosed late, i.e., at clinical stages III-IV. As a result, despite modern surgical techniques and oncological treatments, the survival rate remains below 40–60% due to frequent lymph node metastases and local tumour recurrence. There is a growing concern that diet and inflammatory dietary components may influence the initiation and development of HNSCC. The inflammatory potential of diets can be quantified by the Dietary Inflammatory Index (DII). The DII was derived from an analysis of 45 dietary constituents that either increase or decrease inflammation. Several recent clinical studies have noted a significant relationship between DII score and many inflammation-associated chronic diseases, such as obesity, cardiovascular and neurodegenerative disorders, and diabetes, and the incidence of various human cancers, i.e., prostate, ovarian, breast, colorectal cancer, and HNC. However, few studies have investigated the relationship between DII and HNSCC, with most being limited to observational, case-control, and cross-sectional studies. Therefore, the aim of this narrative review is to present the substantial oncological aspects of DII, discuss the use of DII and its modification, the Energy-Adjusted Dietary Inflammatory Index (E-DII), as indicators of HNSCC risk. It also introduces key diet-induced pro- and anti-inflammatory mechanisms and the cellular molecular signalling pathways determining the carcinogenesis of HNSCC. It provides a comprehensive overview of the current literature, including key opinion-forming systematic reviews, as well as molecular, observational, cross-sectional and case-control studies, all of which are accessible via scholarly databases such as PubMed/EMBASE/Web of Science. Thus, the work serves as a compendium of up-to-date knowledge on the relationship between DII/ED-II score and HNSCC etiopathogenesis and the influence of a diet-induced persistent inflammatory microenvironment. Full article

Obesity and obesity-associated hepatic steatosis represent major metabolic health challenges, yet effective pharmacological interventions remain limited. Rosmarinic acid (RA), a natural polyphenol, has been reported to exert anti-obesity effects; however, its specific roles in restoring hepatic lipid homeostasis and modulating glucose metabolism under diet-induced obesity remain unclear. In this study, we investigated the metabolic effects and underlying mechanisms of RA in mice with high-fat diet (HFD)-induced obesity. RA significantly reduced body weight gain and adipose tissue mass without altering total energy intake, accompanied by increased nocturnal energy expenditure and fecal lipid excretion. RA restored hepatic lipid homeostasis by improving circulating lipid profiles and markedly attenuating hepatic steatosis, fibrosis, and hepatocellular injury. These effects were associated with increased fecal lipid excretion, suppression of hepatic lipogenesis, and enhancement of fatty acid oxidation-related markers. Furthermore, RA reduced fasting blood glucose levels and modulated the expression of hepatic glucose metabolism-related genes. Pancreatic immunohistochemistry showed morphological changes in insulin-positive and glucagon-positive cells following RA supplementation. Collectively, these findings indicate that RA ameliorates obesity-associated metabolic disturbances and hepatic steatosis through coordinated regulation of lipid metabolism and hepatic glucose metabolism-related pathways, highlighting its potential relevance for obesity-associated fatty liver conditions. Full article

Thioredoxin domain-containing protein 5 (TXNDC5) plays a role in diseases related to oxidative stress, energy metabolism, and cellular inflammation. This protein has also been associated with diabetes and insulin folding. To gain insight into these relationships, glucose metabolism was characterized using Txndc5-deficient mice. The absence of TXNDC5 lowered glycemia, which was correlated with higher non-esterified fatty acid (NEFA) levels following an overnight fast on a chow diet in males. Several tolerance tests (pyruvate, glucose, and insulin) revealed no impairment in gluconeogenesis, but rather, higher insulin sensitivity. In vitro assays using an engineered hepatic cell line corroborated the results of increased glucose uptake. When a high-fat, high-sucrose diet was administered to induce a prediabetic state, the absence of TXNDC5 reproduced the lower glycemia and higher NEFA levels observed in mice consuming the chow diet. However, higher levels of plasma insulin were observed in Txndc5-deficient mice. The insulin receptor was increased in the hepatic plasma membranes. Increased hepatic gene expression of G6pc, Irs2, and Igfbp1 was also observed in the absence of TXNDC5. These results indicate that TXNDC5 plays a role in the hepatic sex-differential handling of glucose and lipids, and in retaining the insulin receptor on the plasma membrane. Full article

Obesity is characterized by pathological adipose tissue expansion and dysregulated energy homeostasis. In this study, we examined whether KBN2201 attenuates high-fat diet (HFD)-induced obesity-associated phenotypes and whether these effects are accompanied by changes in appetite-regulatory markers. C57BL/6J mice were fed a normal chow diet or HFD and orally administered vehicle or KBN2201 (20 mg/kg/day) for 12 weeks. In male mice, KBN2201 reduced HFD-induced body weight gain, adipose tissue accumulation, and adipocyte hypertrophy. KBN2201 was also associated with lower cage-level caloric intake under HFD-fed conditions. In epididymal white adipose tissue (eWAT), KBN2201 suppressed Srebf1 expression and reduced HFD-induced increases in Tnf and Tgfb1 expression. In the colon, KBN2201 further increased Pyy mRNA expression, and a positive mRNA-level association was observed between colonic Pyy and Npy2r expression in NTS-containing brainstem tissue. Behavioral analyses provided no evidence of overt locomotor suppression under the present experimental conditions. These findings suggest that KBN2201 attenuates HFD-induced obesity-associated phenotypes in male mice, accompanied by a lower cage-level food intake pattern, reduced adipose tissue expansion, and changes in the expression of colonic Pyy and NTS-containing brainstem Npy2r. Full article

Apolipoprotein A-IV (ApoA-IV) is a glycoprotein secreted by the small intestine to regulate lipid metabolism and satiety. Its role in insulin-independent glucose homeostasis remains largely unknown. In this study, we demonstrate that intestinal ApoA-IV overexpression significantly attenuates diet-induced obesity and hyperglycemia following severe β-cell loss. Over a 20-week high-fat diet challenge, ApoA-IV transgenic (ApoA-IV-Tg) mice maintained significantly lower adiposity than wild-type controls, driven by elevated energy expenditure and fatty acid oxidation rather than reduced caloric intake. Beyond weight maintenance, ApoA-IV maintained excellent systemic glycemic control and enhanced peripheral insulin sensitivity. Most notably, ApoA-IV significantly attenuated hyperglycemia following streptozotocin (STZ)-induced β-cell ablation, maintaining glucose stability despite severe insulin deficiency. Mechanistically, this protection results from a blunted glucagon response and the subsequent suppression of the hepatic pCREB-G6Pase gluconeogenic signaling pathway. In vitro evidence confirms that ApoA-IV directly inhibits pancreatic α-cell glucagon secretion through an LDL receptor-related protein 1 (LRP1)-dependent pathway, reinforced by the precise co-localization of LRP1 and glucagon in pancreatic islets. Furthermore, ApoA-IV-Tg mice were protected from the STZ-induced corticosterone surge and systemic lipolysis. Collectively, these findings establish the ApoA-IV–LRP1 signaling axis as a potent metabolic switch, providing a promising insulin-independent strategy for managing obesity and diabetes. Full article

Malignant tumors require substantial energy sources for proliferation, and dietary composition may influence colorectal carcinogenesis through metabolic and microbiome-related mechanisms. This study investigated the association of low-carbohydrate high-fat dietary patterns with macroscopic tumor burden, morphologic inflammatory cell infiltration, and gut microbiome alterations using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colitis-associated colorectal cancer. Male C57BL/6 mice received AOM followed by three cycles of DSS and were fed a standard diet (SD), high-carbohydrate diet (HCD), low-carbohydrate high-fat lard-based diet (HFL), or low-carbohydrate high-fat coconut oil-based diet (HFC). Body weight, colon length, splenic weight, macroscopic tumor formation, hematoxylin and eosin (H&E)-based inflammatory cell infiltration, and gut microbiome composition were analyzed. The HFL and HFC groups exhibited higher body weights and relatively preserved colon lengths compared with the SD and HCD groups. Tumor number and total tumor size were reduced in the HFL and HFC groups. Total lymphocyte-like inflammatory cell infiltration was not increased in the high-fat diet groups, whereas per-tumor values were interpreted cautiously because they are affected by tumor number. Gut microbiome analysis demonstrated altered microbial composition, increased alpha diversity, and distinct temporal microbial dynamics in the high-fat diet groups. Because the HFL and HFC diets simultaneously changed carbohydrate content, fat content, fat source, and caloric density, these findings should be interpreted as exploratory effects of low-carbohydrate high-fat dietary patterns rather than independent effects of carbohydrate restriction, total fat, or fat source. Full article

Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10–20 µg/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management. Full article

Background/Objectives: Retinoic acids (RA) are involved in regulation of weight and energy metabolism. Mice lacking a RA synthesis enzyme, ALDH1A1, are resistant to diet-induced obesity. We previously identified an ALDH1A1-specific inhibitor, FSI-TN42 (N42), and demonstrated its efficacy in suppressing weight gain in male C57BL/6 mice fed a high-fat diet (HFD). In this report, we evaluated whether N42 is similarly effective in female mice. Methods: Two studies were performed. In the first study, C57BL/6 female mice were fed a HFD for 12 weeks to induce obesity, after which half were switched to a HFD supplemented with N42 (1 g/kg diet). A control group of mice was maintained on a low-fat purified diet throughout the study. Body weight was determined weekly, and fasting or fed blood glucose was determined at 4–8-week intervals. In the second study, obese female C57BL/6 mice were transitioned from a HFD to either (1) a moderate-fat diet (MFD) or (2) MFD + N42 for 9 weeks. Results: N42 significantly suppressed weight gain in female mice maintained on a HFD. However, it did not enhance weight loss when administered alongside a MFD diet, which alone induced significant weight loss comparable to mice fed a control diet throughout the study. Conclusions: The ALDH1A1 inhibitor N42 suppresses weight gain in female mice, consistent with prior findings in male mice. However, unlike in males, N42 did not enhance weight loss under conditions of caloric reduction, likely due to more profound weight loss induced by the lower-calorie diet in female mice. Full article