Lipid Metabolism and its Mechanism Triggered by Supercritical CO2 Extract of Adlay (Coix lacryma-jobi var. ma-yuen (Rom. Caill.) Stapf) Bran in High-Fat Diet Induced Hyperlipidemic Hamsters

Adlay (Coix lacryma-jobi var. ma-yuen (Rom. Caill.) Stapf) seeds are edible crop classified as Traditional Chinese Medicine (TCM). Adlay bran (AB) is one of the wastes generated during adlay refining processes. In this work, supercritical fluid extract of AB (AB-SCF) was investigated to reveal its lipid regulating potential and decode its bifunctional ingredients. AB-SCF×0.5 (30.84 mg/kg/body weight), AB-SCF×1 (61.67 mg/kg/BW), AB-SCF×5 (308.35 mg/kg/BW) and AB-SCF×10 (616.70 mg/kg/BW) were administrated to high fat-diet (HFD) induced hyperglycemic hamsters for 8 weeks. The results indicates that AB-SCF displays a prevention of dramatic body weight gains, lower levels of serum TG, TC, LDL-C and higher in HDL-C, amelioration of cardiovascular risk, alleviation of hepatic TG, TC and lipid peroxidation, and enhancement on cholesterol metabolism with higher bile acid excretion. Investigations on energy metabolic mechanism demonstrates that the hyperlipidemia mitigating capacities of AB-SCF are up-regulated on lipoprotein lipase, AMPK, p-AMPK and down-regulated at fatty acid synthase. Major bio-functional lipid compositions are identified as linoleic acid (28.59%) and oleic acid (56.95%). Non-lipid chemical and active markers are confirmed as 3-O-(trans-4-feruloyl)-β-sitostanol (1463.42 ppm), 3-O-(cis-4-feruloyl)-β-sitostanol (162.60 ppm), and β-sitosterol (4117.72 ppm). These compositions might synergistically responsible for the mentioned activities and can be regarded as analytical targets in quality control. AB-SCF may be considered as a promising complementary supplement, and developed as a functional food or new botanical drug in the future.

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Cyanidin-3-O-Galactoside-Enriched Aronia melanocarpa Extract Attenuates Weight Gain and Adipogenic Pathways in High-Fat Diet-Induced Obese C57BL/6 Mice

Nutrients ◽

10.3390/nu11051190 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1190 ◽

Cited By ~ 9

Author(s):

Su-Min Lim ◽

Hyun Sook Lee ◽

Jae In Jung ◽

So Mi Kim ◽

Nam Young Kim ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Peroxisome Proliferator ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor ◽

Aronia Melanocarpa

Aronia melanocarpa are a rich source of anthocyanins that have received considerable interest for their relations to human health. In this study, the anti-adipogenic effect of cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract (AM-Ex) and its underlying mechanisms were investigated in an in vivo system. Five-week-old male C57BL/6N mice were randomly divided into five groups for 8-week feeding with a control diet (CD), a high-fat diet (HFD), or a HFD with 50 (AM-Ex 50), 100 (AM-Ex 100), or 200 AM-Ex (AM-Ex 200) mg/kg body weight/day. HFD-fed mice showed a significant increase in body weight compared to the CD group, and AM-Ex dose-dependently inhibited this weight gain. AM-Ex significantly reduced the food intake and the weight of white fat tissue, including epididymal fat, retroperitoneal fat, mesenteric fat, and inguinal fat. Treatment with AM-Ex (50 to 200 mg/kg) reduced serum levels of leptin, insulin, triglyceride, total cholesterol, and low density lipoprotein (LDL)-cholesterol. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that AM-Ex suppressed adipogenesis by decreasing CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma coactivator-1α, acetyl-CoA carboxylase 1, ATP-citrate lyase, fatty acid synthase, and adipocyte protein 2 messenger RNA (mRNA) expressions. These results suggest that AM-Ex is potentially beneficial for the suppression of HFD-induced obesity by modulating multiple pathways associated with adipogenesis and food intake.

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Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1

Nutrients ◽

10.3390/nu11102475 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2475 ◽

Cited By ~ 6

Author(s):

Hyun Sook Lee ◽

Su-Min Lim ◽

Jae In Jung ◽

So Mi Kim ◽

Jae Kyoung Lee ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Regulatory Element ◽

Control Diet ◽

Sirtuin 1 ◽

Hormone Sensitive Lipase ◽

High Fat ◽

Gynostemma Pentaphyllum

Gynostemma pentaphyllum is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism of G. pentaphyllum extract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.

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Mice deleted for GPAT3 have reduced GPAT activity in white adipose tissue and altered energy and cholesterol homeostasis in diet-induced obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00666.2013 ◽

2014 ◽

Vol 306 (10) ◽

pp. E1176-E1187 ◽

Cited By ~ 29

Author(s):

Jingsong Cao ◽

Sylvie Perez ◽

Bryan Goodwin ◽

Qingcong Lin ◽

Haibing Peng ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

White Adipose Tissue ◽

High Fat Diet ◽

Cholesterol Metabolism ◽

Body Weight Gain ◽

Cholesterol Homeostasis ◽

High Fat

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the synthesis of glycerolipids and glycerophospholipids. Microsomal GPAT, the major GPAT activity, is encoded by at least two closely related genes, GPAT3 and GPAT4. To investigate the in vivo functions of GPAT3, we generated Gpat3-deficient ( Gpat3 −/−) mice. Total GPAT activity in white adipose tissue of Gpat3 −/− mice was reduced by 80%, suggesting that GPAT3 is the predominant GPAT in this tissue. In liver, GPAT3 deletion had no impact on total GPAT activity but resulted in a 30% reduction in N-ethylmaleimide-sensitive GPAT activity. The Gpat3 −/− mice were viable and fertile and exhibited no obvious metabolic abnormalities on standard laboratory chow. However, when fed a high-fat diet, female Gpat3 −/− mice showed decreased body weight gain and adiposity and increased energy expenditure. Increased energy expenditure was also observed in male Gpat3 −/− mice, although it was not accompanied by a significant change in body weight. GPAT3 deficiency lowered fed, but not fasted, glucose levels and tended to improve glucose tolerance in diet-induced obese male and female mice. On a high-fat diet, Gpat3 −/− mice had enlarged livers and displayed a dysregulation in cholesterol metabolism. These data establish GPAT3 as the primary GPAT in white adipose tissue and reveal an important role of the enzyme in regulating energy, glucose, and lipid homeostasis.

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Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90248.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. E904-E912 ◽

Cited By ~ 123

Author(s):

Galyna Bryzgalova ◽

Lovisa Lundholm ◽

Neil Portwood ◽

Jan-Åke Gustafsson ◽

Akhtar Khan ◽

...

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

Plasma Levels ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Molecular Mechanisms ◽

Target Genes ◽

High Fat ◽

Expression Levels ◽

Hepatic Expression

The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17β-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E2, given daily (50 μg/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2 treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor α and SREBP1c were not changed by E2 treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2 decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2 treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.

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Hypolipidemic and Hepatoprotective Effects of Polysaccharides Extracted from Liriope spicata Var. Prolifera in C57BL/6J Mice with High-Fat Diet-Induced Hyperlipidemia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8013189 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yi-Hui Liu ◽

Zhi-Nan Xiang ◽

Chen Chen ◽

Luo-Sheng Wan ◽

Jia-Chun Chen

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Bile Acid Metabolism ◽

Peroxisome Proliferator ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor ◽

Hepatoprotective Effects

In this study, C57BL/6J mice with high-fat diet- (HFD-) induced hyperlipidemia were treated with total Liriope spicata var. prolifera polysaccharides (TLSP: 200, 400, and 800 mg/kg body weight), simvastatin (3 mg/kg body weight), or saline for 8 weeks, respectively. The results showed that TLSP had strong lipid-lowering and hepatoprotective effects on C57BL/6J mice with HFD-induced hyperlipidemia. TLSP administration significantly reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels and downregulated the expressions of peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase (FAS) in the adipose and liver tissues of the mice. TLSP exerted hypolipidemic and hepatoprotective effects by activating lipid/bile acid metabolism via the FXH-SHP/CYP7A1 and SEBP-1c/FAC/ACC signaling pathways. Thus, TLPS is a promising natural polymer with hepatoprotective and hypolipidemic properties.

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Abstract 19498: Scavenger Receptor BI (SR-BI) Deficiency Uncouples Obesity From Glucose Intolerance in Mice

Circulation ◽

10.1161/circ.132.suppl_3.19498 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Menno Hoekstra ◽

Amber B Ouweneel ◽

Miranda Van Eck

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

Glucose Intolerance ◽

High Fat Diet ◽

Cholesterol Metabolism ◽

Scavenger Receptor ◽

Oral Glucose ◽

High Fat ◽

Scavenger Receptor Bi ◽

Obesity In Mice

Introduction: Scavenger receptor BI (SR-BI) is a multi-purpose player in cholesterol metabolism. Interestingly, several studies in humans have suggested that a significant relationship exists between the presence of common variants in the SR-BI gene and a higher body mass index. We therefore evaluated the contribution of SR-BI to high fat diet-induced obesity in mice. Methods and Results: Male SR-BI knockout (SR-BI KO; N=10) and wild-type (WT; N=9) mice were fed a diet containing 45% energy as fat for 12 weeks. SR-BI KO mice exhibited a worsened metabolic plasma profile as compared to WT controls with higher fasting levels of free cholesterol (+111%; P<0.001), cholesterol esters (+84%; P<0.001), triglycerides (+40%; P<0.01), and glucose (+20%; P<0.01). Daily food intake was similar in the two types of mice; 4.5±0.3 g for SR-BI KO vs 4.1±0.3 g for WT. Importantly, the relative increase in body weight over time was significantly greater in SR-BI KO mice (+51%) as compared to WT controls (+33%; two-way ANOVA P<0.001 for genotype). The exacerbated increase in body weight could be attributed to a higher white adipose tissue mass (correlation coefficient R=0.87; P<0.001). High fat diet-fed WT mice were glucose intolerant, but remained resistant to atherosclerosis. In contrast, atherosclerotic lesions could be readily detected in the aortic root of SR-BI KO mice (6.9±1.5 x 10 3 μm 2 ; P<0.001), while their glucose tolerance was remarkably higher compared to that of controls (oral glucose tolerance test AUC 484±68 mM.min for SR-BI KO vs 875±130 mM.min for WT; P<0.05). SR-BI deficiency thus uncouples obesity from glucose intolerance in mice. Conclusions: Our studies for the first time show that a proper SR-BI function inhibits the development of obesity in mice. Furthermore, these data imply that SR-BI may serve as therapeutic target to overcome the glucose intolerance normally associated with the presence of (morbid) obesity.

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Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet

Nutrients ◽

10.3390/nu12123753 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3753

Author(s):

Hang-Hee Cho ◽

Soo-Jung Lee ◽

Sung-Ho Kim ◽

Sun-Hee Jang ◽

Chungkil Won ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Fatty Acid ◽

Lipid Accumulation ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Binding Protein ◽

High Fat ◽

Fatty Acid Binding ◽

Obese Rats

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3–isobutyl–1–methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3β (GSK3β) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

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Effects of dietary high fructose corn syrup on regulation of energy intake and leptin gene expression in rats

Revista de Nutrição ◽

10.1590/1415-52732015000600003 ◽

2015 ◽

Vol 28 (6) ◽

pp. 597-605 ◽

Cited By ~ 1

Author(s):

Guadalupe López-Rodríguez ◽

Silke Kotasek Osuna ◽

Marcos Galván García ◽

Teodoro Suárez Dieguez

Keyword(s):

Gene Expression ◽

Body Weight ◽

High Fat Diet ◽

Wistar Rats ◽

Fatty Acid Synthase ◽

High Fructose Corn Syrup ◽

High Fat ◽

Corn Syrup ◽

High Fructose ◽

The Brain

OBJECTIVE: To evaluate in Wistar rats the effect of chronic use of high fructose corn syrup on serum lipids, body weight, energy intake regulation, and expression of associated genes. METHODS: For 11 weeks, male rats were fed a standard diet with either water (control) or 15% high fructose corn syrup solution, or fed a high-fat diet. The rats' food intake and body weight were measured weekly. Expression of leptin and fatty acid synthase genes was quantified in their brain and adipose tissue upon sacrifice at age 119 days using real-time polymerase chain reaction. RESULTS: The intake of 15% high fructose corn syrup did not affect the rats' weight, only the rats on the high-fat diet gained significant weight. The rats in both diets had lower levels of leptin expression and high levels of fatty acid synthase in the brain, which were associated with high serum triglycerides. CONCLUSION: Fifteen percent high fructose corn syrup intake and the high-fat diet reduced leptin gene expression in the brain of Wistar rats, with differential effects on weight gain.

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