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14 pages, 5867 KiB

Open AccessArticle

Anti-Obesity Effects of GABA in C57BL/6J Mice with High-Fat Diet-Induced Obesity and 3T3-L1 Adipocytes

by Heegu Jin, Hyein Han, Gunju Song, Hyun-Ji Oh and Boo-Yong Lee

Int. J. Mol. Sci. 2024, 25(2), 995; https://doi.org/10.3390/ijms25020995 - 13 Jan 2024

Cited by 1 | Viewed by 959

Abstract

Obesity is the excessive accumulation of body fat resulting from impairment in energy balance mechanisms. In this study, we aimed to investigate the mechanism whereby GABA (γ-aminobutyric acid) prevents high-fat diet-induced obesity, and whether it induces lipolysis and browning in white adipose tissue [...] Read more.

Obesity is the excessive accumulation of body fat resulting from impairment in energy balance mechanisms. In this study, we aimed to investigate the mechanism whereby GABA (γ-aminobutyric acid) prevents high-fat diet-induced obesity, and whether it induces lipolysis and browning in white adipose tissue (WAT), using high-fat diet (HFD)-fed obese mice and 3T3-L1 adipocytes. We demonstrated that GABA substantially inhibits the body mass gain of mice by suppressing adipogenesis and lipogenesis. Consistent with this result, histological analysis of WAT demonstrated that GABA decreases adipocyte size. Moreover, we show that GABA administration decreases fasting blood glucose and improves serum lipid profiles and hepatic lipogenesis in HFD-fed obese mice. Furthermore, Western blot and immunofluorescence analyses showed that GABA activates protein kinase A (PKA) signaling pathways that increase lipolysis and promote uncoupling protein 1 (UCP1)-mediated WAT browning. Overall, these results suggest that GABA exerts an anti-obesity effect via the regulation of lipid metabolism. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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12 pages, 2896 KiB

Open AccessArticle

Inhibitory Effects of Loganin on Adipogenesis In Vitro and In Vivo

by Hyoju Jeon, Chang-Gun Lee, Hyesoo Jeong, Seong-Hoon Yun, Jeonghyun Kim, Laxmi Prasad Uprety, Kang-Il Oh, Shivani Singh, Jisu Yoo, Eunkuk Park and Seon-Yong Jeong

Int. J. Mol. Sci. 2023, 24(5), 4752; https://doi.org/10.3390/ijms24054752 - 1 Mar 2023

Cited by 2 | Viewed by 2078

Abstract

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) [...] Read more.

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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16 pages, 2626 KiB

Open AccessArticle

Cyclopia intermedia (Honeybush) Induces Uncoupling Protein 1 and Peroxisome Proliferator-Activated Receptor Alpha Expression in Obese Diabetic Female db/db Mice

by Babalwa Unice Jack, Pritika Ramharack, Christiaan Malherbe, Kwazi Gabuza, Elizabeth Joubert and Carmen Pheiffer

Int. J. Mol. Sci. 2023, 24(4), 3868; https://doi.org/10.3390/ijms24043868 - 15 Feb 2023

Cited by 3 | Viewed by 1701

Abstract

Previously, we reported that a crude polyphenol-enriched fraction of Cyclopia intermedia (CPEF), a plant consumed as the herbal tea, commonly known as honeybush, reduced lipid content in 3T3-L1 adipocytes and inhibited body weight gain in obese, diabetic female leptin receptor-deficient (db/db) mice. In [...] Read more.

Previously, we reported that a crude polyphenol-enriched fraction of Cyclopia intermedia (CPEF), a plant consumed as the herbal tea, commonly known as honeybush, reduced lipid content in 3T3-L1 adipocytes and inhibited body weight gain in obese, diabetic female leptin receptor-deficient (db/db) mice. In the current study, the mechanisms underlying decreased body weight gain in db/db mice were further elucidated using western blot analysis and in silico approaches. CPEF induced uncoupling protein 1 (UCP1, 3.4-fold, p < 0.05) and peroxisome proliferator-activated receptor alpha (PPARα, 2.6-fold, p < 0.05) expression in brown adipose tissue. In the liver, CPEF induced PPARα expression (2.2-fold, p < 0.05), which was accompanied by a 31.9% decrease in fat droplets in Hematoxylin and Eosin (H&E)-stained liver sections (p < 0.001). Molecular docking analysis revealed that the CPEF compounds, hesperidin and neoponcirin, had the highest binding affinities for UCP1 and PPARα, respectively. This was validated with stabilising intermolecular interactions within the active sites of UCP1 and PPARα when complexed with these compounds. This study suggests that CPEF may exert its anti-obesity effects by promoting thermogenesis and fatty acid oxidation via inducing UCP1 and PPARα expression, and that hesperidin and neoponcirin may be responsible for these effects. Findings from this study could pave the way for designing target-specific anti-obesity therapeutics from C. intermedia. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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17 pages, 3830 KiB

Open AccessArticle

Mangiferin Ameliorates Obesity-Associated Inflammation and Autophagy in High-Fat-Diet-Fed Mice: In Silico and In Vivo Approaches

by Ji-Won Noh, Han-Young Lee and Byung-Cheol Lee

Int. J. Mol. Sci. 2022, 23(23), 15329; https://doi.org/10.3390/ijms232315329 - 5 Dec 2022

Cited by 6 | Viewed by 1676

Abstract

Obesity-induced insulin resistance is the fundamental cause of metabolic syndrome. Accordingly, we evaluated the effect of mangiferin (MGF) on obesity and glucose metabolism focusing on inflammatory response and autophagy. First, an in silico study was conducted to analyze the mechanism of MGF in [...] Read more.

Obesity-induced insulin resistance is the fundamental cause of metabolic syndrome. Accordingly, we evaluated the effect of mangiferin (MGF) on obesity and glucose metabolism focusing on inflammatory response and autophagy. First, an in silico study was conducted to analyze the mechanism of MGF in insulin resistance. Second, an in vivo experiment was conducted by administering MGF to C57BL/6 mice with high-fat-diet (HFD)-induced metabolic disorders. The in silico analysis revealed that MGF showed a high binding affinity with macrophage-related inflammatory cytokines and autophagy proteins. In the in vivo study, mice were divided into three groups: normal chow, HFD, and HFD + MGF 150 mg/kg. MGF administration to obese mice significantly improved the body weight, insulin-sensitive organs weights, glucose and lipid metabolism, fat accumulation in the liver, and adipocyte size compared to HFD alone. MGF significantly reduced the macrophages in adipose tissue and Kupffer cells, inhibited the gene expression ratio of tumor necrosis factor-α and F4/80 in adipose tissue, reduced the necrosis factor kappa B gene, and elevated autophagy-related gene 7 and fibroblast growth factor 21 gene expressions in the liver. Thus, MGF exerted a therapeutic effect on metabolic diseases by improving glucose and lipid metabolism through inhibition of the macrophage-mediated inflammatory responses and activation of autophagy. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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16 pages, 2567 KiB

Open AccessArticle

Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice

by Ji-Won Kim, Young-Mo Yang, Eun-Young Kwon and Ji-Young Choi

Int. J. Mol. Sci. 2022, 23(16), 9295; https://doi.org/10.3390/ijms23169295 - 18 Aug 2022

Cited by 1 | Viewed by 1911

Abstract

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation [...] Read more.

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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25 pages, 1369 KiB

Open AccessReview

New Therapeutic Strategies for Obesity and Its Metabolic Sequelae: Brazilian Cerrado as a Unique Biome

by Tamaeh Monteiro-Alfredo, Maria Lígia Rodrigues Macedo, Kely de Picoli Souza and Paulo Matafome

Int. J. Mol. Sci. 2023, 24(21), 15588; https://doi.org/10.3390/ijms242115588 - 25 Oct 2023

Viewed by 1188

Abstract

Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been [...] Read more.

Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been described by several studies associating ethnopharmacological knowledge with phytochemical compounds and therapeutic effects. Based on this wide range of options, the Brazilian population has been using these medicinal plants (MP) for centuries for the treatment of various health conditions. Among these, we highlight metabolic diseases, namely obesity and its metabolic alterations from metabolic syndrome to later stages such as type 2 diabetes (T2D). Several studies have shown that adipose tissue (AT) dysfunction leads to proinflammatory cytokine secretion and impaired free fatty acid (FFA) oxidation and oxidative status, creating the basis for insulin resistance and glucose dysmetabolism. In this scenario, the great Brazilian biodiversity and a wide variety of phytochemical compounds make it an important candidate for the identification of pharmacological strategies for the treatment of these conditions. This review aimed to analyze and summarize the current literature on plants from the Brazilian Cerrado that have therapeutic activity against obesity and its metabolic conditions, reducing inflammation and oxidative stress. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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24 pages, 3372 KiB

Open AccessReview

A Review of the Anti-Obesity Effects of Wild Edible Plants in the Mediterranean Diet and Their Active Compounds: From Traditional Uses to Action Mechanisms and Therapeutic Targets

by Bashar Saad

Int. J. Mol. Sci. 2023, 24(16), 12641; https://doi.org/10.3390/ijms241612641 - 10 Aug 2023

Cited by 6 | Viewed by 2181

Abstract

Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some [...] Read more.

Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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23 pages, 1098 KiB

Open AccessReview

Fermented Foods in the Management of Obesity: Mechanisms of Action and Future Challenges

by Mahsa Jalili, Maryam Nazari and Faidon Magkos

Int. J. Mol. Sci. 2023, 24(3), 2665; https://doi.org/10.3390/ijms24032665 - 31 Jan 2023

Cited by 7 | Viewed by 3595

Abstract

Fermented foods are part of the staple diet in many different countries and populations and contain various probiotic microorganisms and non-digestible prebiotics. Fermentation is the process of breaking down sugars by bacteria and yeast species; it not only enhances food preservation but can [...] Read more.

Fermented foods are part of the staple diet in many different countries and populations and contain various probiotic microorganisms and non-digestible prebiotics. Fermentation is the process of breaking down sugars by bacteria and yeast species; it not only enhances food preservation but can also increase the number of beneficial gut bacteria. Regular consumption of fermented foods has been associated with a variety of health benefits (although some health risks also exist), including improved digestion, enhanced immunity, and greater weight loss, suggesting that fermented foods have the potential to help in the design of effective nutritional therapeutic approaches for obesity. In this article, we provide a comprehensive overview of the health effects of fermented foods and the corresponding mechanisms of action in obesity and obesity-related metabolic abnormalities. Full article

(This article belongs to the Special Issue Natural Products in Obesity: Novel Strategies and Molecular Mechanisms)

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