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

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.

Aurantio-obtusin improves obesity and insulin resistance induced by high-fat diet in obese mice.

Aurantio-obtusin (AUR) is the main bioactive compound among the anthraquinones, from Cassia seed extract. This study was conducted to identify whether AUR could improve obesity and insulin resistance, induced by a high-fat diet in obese mice. Mice were fed a high-fat diet for 6 weeks and were then assigned to the high-fat diet (HFD) control group, the AUR 5 mg/kg group, or the AUR 10 mg/kg group. AUR improves glucose by activating the expression of PI3K, Akt and GLUT4, GLUT2. AUR altered the expression levels of several lipid metabolism-related and adipokine genes. AUR decreased the mRNA expression of PPAR-γ, FAS and increased the mRNA expression of PPAR-α in liver. AUR lowered SREBP-1c, FAS, SCD-1, inflammatory cytokines, and increased the expression of PPAR-γ, PPAR-α, CPT-1, and adiponectin in white adipose tissue (WAT). AUR docking with the insulin receptor showed that the residues of the insulin receptor, ectodomain, were the same as those around the emodin. The effect of AUR may be elicited by regulating the activity of the insulin signaling pathway, expression of lipid metabolism-related genes, and expression of inflammatory cytokine markers to improve adiposity, insulin resistance, and dyslipidemia.

Effect of the Capsicoside G-rich Fraction from Pepper (Capsicum annuum L.) Seeds on High-fat Diet-induced Obesity in Mice.

Obesity is one of the most common metabolic syndromes and is a major threat to human health worldwide. Given the size of this problem, there is growing interest in natural agents that may decrease obesity. In this study, we investigated the anti-obesity effect of a capsicoside G-rich fraction (CRF; 13.35% capsicoside G) isolated from pepper seeds in diet-induced obese mice. C57BL/6J mice were fed either a normal diet or a high-fat diet (HFD), with or without CRF (HFD + CRF; 10 and 100 mg/kg body weight). The body weight and food efficiency ratio of mice fed HFD + CRF were lower in comparison to that of mice fed only an HFD. Epididymal adipose tissue weight and adipocyte hypertrophy were significantly lower in HFD + CRF mice than in HFD mice. The fat deposition in the liver of mice fed HFD + CRF was lower compared to that of mice fed only an HFD. CRF significantly reversed the HFD-induced elevation of the expression of key adipocyte differentiation regulators, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, sterol regulatory element binding protein 1c, and their target genes. These results suggest that CRF could be used as dietary therapy for the prevention of obesity and obesity-related metabolic diseases. Copyright © 2016 John Wiley & Sons, Ltd.

Pea-Resistant Starch with Different Multi-scale Structural Features Attenuates the Obesity-Related Physiological Changes in High-Fat Diet Mice.

The present study compared the modulatory effects of different resistant starches (RSs) isolated from native (NP-RS), acid-hydrolyzed (AHP-RS), and pullulanase debranched (PDP-RS) pea starches on the corresponding in vivo metabolic responses in high fat (HF)-diet-induced obese mice. The biochemical studies on serum lipid profile and antioxidant enzyme activities were supported by histological and gene expression analyses, which suggested a potential therapeutic role for RS in regulating obesity, possibly through the production of short-chain fatty acids and the proliferation of some beneficial colonic bacteria, including Allobaculum, Bifidobacterium, Odoribacter, Clostridium, and Prevotella. Particularly, a more pronounced effect of AHP-RS with a higher proportion of the crystalline region and a more ordered double-helical alignment on improving the hyperlipidemic symptoms in obese mice induced by a HF diet was observed. Our analysis revealed that the RS3 samples seemed to be more effective than RS2 in terms of attenuating obesity in mice that were fed a HF diet.

Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice.

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (-39.1%) and fat weight (-26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (-20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder's functional and health-promoting benefits associated with anti-obesity and antidiabetes.

Black Raspberry Seed Oil Improves Lipid Metabolism by Inhibiting Lipogenesis and Promoting Fatty-Acid Oxidation in High-Fat Diet-Induced Obese Mice and db/db Mice.

The objective of this study was to evaluate the beneficial effect of α-linolenic acid-rich black raspberry seed (BRS) oil on lipid metabolism in high-fat diet (HFD)-induced obese and db/db mice. Five-week-old C57BL/6 mice were fed diets consisting of 50% calories from lard, 5% from soybean, and 5% from corn oil (HFD), or 50% calories from lard and 10% from BRS oil (HFD + BRS oil diet) for 12 weeks. Six-week-old C57BL/KsJ-db/db mice were fed diets consisting of 16% calories from soybean oil (standard diet), 8% from soybean, and 8% from BRS oil, or 16% from BRS oil for 10 weeks. The BRS oil diets lowered the levels of triacylglycerol, nonesterified fatty acids, and total cholesterol in serum and liver of both of the obese and db/db mice as compared with the HFD and standard diet, respectively. mRNA levels of lipogenesis markers including cluster of differentiation 36, fatty-acid-binding protein 1, sterol regulatory element binding protein 1c, fatty-acid synthase, and solute carrier family 25 member 1 in the liver of the BRS oil groups were lower than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. On the other hand, fatty-acid oxidation markers including carnitine palmitoyltransferase 1A, acyl-CoA dehydrogenase, hydroxylacyl-CoA dehydrogenase α, and acyl-CoA oxidase in the liver of the BRS oil groups were higher than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. Peroxisome proliferator-activated receptor α mRNA and protein levels increased in the liver and epididymal adipose tissue of the obese and db/db mice fed BRS oil compared with HFD and standard diet, respectively. BRS oil might improve lipid metabolism by inhibiting lipogenesis and promoting fatty-acid oxidation in HFD-induced obese and db/db mice.

Gelidium elegans Regulates the AMPK-PRDM16-UCP-1 Pathway and Has a Synergistic Effect with Orlistat on Obesity-Associated Features in Mice Fed a High-Fat Diet.

The incidence of obesity is rising at an alarming rate throughout the world and is becoming a major public health concern with incalculable social and economic costs. Gelidium elegans (GENS), also previously known as Gelidium amansii, has been shown to exhibit anti-obesity effects. Nevertheless, the mechanism by which GENS is able to do this remains unclear. In the present study, our results showed that GENS prevents high-fat diet (HFD)-induced weight gain through modulation of the adenosine monophosphate-activated protein kinase (AMPK)-PR domain-containing16 (PRDM16)-uncoupling protein-1 (UCP-1) pathway in a mice model. We also found that GENS decreased hyperglycemia in mice that had been fed a HFD compared to corresponding controls. We also assessed the beneficial effect of the combined treatment with GENS and orlistat (a Food and Drug Administration-approved obesity drug) on obesity characteristics in HFD-fed mice. We found that in HFD-fed mice, the combination of GENS and orlistat is associated with more significant weight loss than orlistat treatment alone. Moreover, our results demonstrated a positive synergistic effect of GENS and orlistat on hyperglycemia and plasma triglyceride level in these animals. Thus, we suggest that a combination therapy of GENS and orlistat may positively influence obesity-related health outcomes in a diet-induced obese population.

Germinated Waxy Black Rice Suppresses Weight Gain in High-Fat Diet-Induced Obese Mice.

This study was performed to investigate the antiobesity effect of germinated waxy black rice (GWBR) in high-fat diet (HFD)-induced obese mice. The mice were divided into a normal diet (ND) group, HFD group, and 2 test groups for 8 weeks: 2.5% GWBR-supplemented (GWBR-2.5) group and 5% GWBR-supplemented (GWBR-5) group. Supplementing with GWBR significantly reduced body weight gain and lipid accumulation in the liver and adipose tissue compared to the HFD control group. Triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol levels in serum were decreased by GWBR supplementation, whereas high-density lipoprotein-cholesterol level significantly increased. In addition, mRNA levels of transcriptional factors, such as peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein (C/EBP)-α, C/EBP-ß, sterol regulatory element-binding protein-1c, and related genes, including adipocyte fatty acid-binding protein, fatty acid synthase, and lipoprotein lipase, were significantly lower in the GWBR groups. However, lipolytic enzymes, such as hormone-sensitive lipase, adipose TG lipase, and carnitine palmitoyltransferase-1, and uncoupling protein 2 mRNA levels were significantly higher in GWBR-supplemented mice. These results suggest that GWBR exerts antiobesity effects by decreasing lipid accumulation and promoting lipolysis in HFD-induced obese mice.

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice.

OBJECTIVES: To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract (GCBE) in high-fat diet (HFD)-induced obese mice. METHODS: Obesity was induced in mice using a HFD for four weeks. Then, mice were fed only HFD or HFD with GCBE at 50, 100, and 200 mg/kg. Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay. Body fat reduction was measured through dual-energy X-ray absorptiometry. RESULTS: In HFD-induced obese mice, GCBE treatment significantly decreased body weight gain, liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones, like adiponectin and leptin. GCBE treatment decreased mRNA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver, and decreased the corresponding protein expression. Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE. GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased. CONCLUSIONS: GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.

Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice.

OBJECTIVE: To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M. pilosus)-fermented black soybean (MFBS) extracts (MFBSE) and MFBS powders (MFBSP) in adipocytes and high-fat diet (HFD)-induced obese mice, respectively. METHODS: Black soybean was fermented with M. pilosus, and the main constituents in MFBS were analyzed by HPLC analysis. In vitro, MFBSE were examined for anti-adipogenic effects using Oil-Red O staining. In vivo, mice were fed a normal-fat diet (NFD) control, HFD control or HFD containing 1 g/kg MFBSP for 12 weeks, and then body weight gain and tissues weight measured. Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects. RESULTS: MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity. MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice. MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes, such as peroxisome proliferator-activated receptor γ(PPAR γ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS), in adipocytes and in white adipose tissue (WAT) of HFD-induced obese mice. CONCLUSIONS: These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFD-induced obese mice.

Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice.

OBJECTIVE: To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in high-fat diet (HFD)-induced obese mice and 3T3-L1 adipocytes. METHODS: The roots of Adenophora triphylla were extracted with 70% ethanol. To demonstrate the compounds, linoleic acid was analyzed by using gas chromatography; and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese mice. RESULTS: Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 adipocytes. Furthermore, 200 and 400 mg/kg ATE treatment significantly decreased the body weight gain, white adipose tissues (WATs) weight and plasma triglyceride level, while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice, as compared with the HFD group. Treatment with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. ATE treatment showed significantly lower expression level of adipogenesis-related proteins, such as peroxisome proliferator-activated receptor γ, fatty acid binding protein (aP2), fatty acid synthase in 3T3-L1 adipocytes; and furthermore, decreased peroxisome proliferator-activated receptor γ, aP2, fatty acid synthase, sterol regulatory element binding protein-1c, and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese mice. CONCLUSIONS: These results suggested that the ATE has an anti-obesity effect, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

Anti-Obesity Effects of the Mixture of Eriobotrya japonica and Nelumbo nucifera in Adipocytes and High-Fat Diet-Induced Obese Mice.

The present study is to evaluate the anti-obesity effects of Eriobotrya japonica (EJ), Nelumbo nucifera (NN), and their mixture (MIX, 1:1 ratio) in 3T3-L1 adipocytes and high-fat diet-induced obese mice. The treatment of EJ, NN, and MIX in 3T3-L1 adipocytes effectively inhibited lipid accumulation, significantly decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP1c), and adipocyte lipid-binding protein (aP2), and significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, oral treatment of MIX showed stronger effects than individual treatment. C57BL/6J mice (6 week old) were divided into two groups; low fat diet (LFD) containing 10% calories from fat and high fat diet (HFD) containing 60% calories from fat. The HFD groups were further divided into five subgroups; treated with distilled water (HFD), treated with 400 mg/kg EJ (EJ400), treated with 400 mg/kg NN (NN400), treated with 200 mg/kg MIX (MIX200), and treated with 400 mg/kg MIX (MIX400) during 13 weeks. In our results, the administration of EJ, NN, and MIX significantly decreased body weight (BW), fat weight, liver weight, hepatic triglyceride (TG) and total cholesterol (TC), lipid droplets in the liver, food efficacy ratio, and the plasma TG, TC, glucose, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in a dose-dependent manner, and MIX treatment showed stronger effect than their individual treatments. Similarly, MIX treatment decreased the expression of PPARγ, SREBP-1c, FAS, and ACC more strongly in the adipose tissue than single treatments. In conclusion, the MIX of EJ and NN extract may strongly regulate BW gain than EJ or NN alone, and its anti-obesity effect is associated with the control of lipid metabolism, including adipogenesis and lipogenesis.