Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK

2010 ◽  
Vol 298 (4) ◽  
pp. C961-C971 ◽  
Author(s):  
Mandeep P. Gaidhu ◽  
Nicole M. Anthony ◽  
Prital Patel ◽  
Thomas J. Hawke ◽  
Rolando B. Ceddia
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Adrenergic Receptor ◽  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Receptor Signaling ◽  
High Fat ◽  
Fat Depots

This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase A2 expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1α expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity.

scholarly journals Regulatory Efficacy of Spirulina platensis Protease Hydrolyzate on Lipid Metabolism and Gut Microbiota in High-Fat Diet-Fed Rats

2018 ◽  
Vol 19 (12) ◽  
pp. 4023 ◽  
Author(s):  
Pengpeng Hua ◽  
Zhiying Yu ◽  
Yu Xiong ◽  
Bin Liu ◽  
Lina Zhao
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Spirulina Platensis ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Public Health Issue ◽  
Peroxisome Proliferator ◽  
Hypolipidemic Effect ◽  
High Fat

Lipid metabolism disorder (LMD) is a public health issue. Spirulina platensis is a widely used natural weight-reducing agent and Spirulina platensis is a kind of protein source. In the present study, we aimed to evaluate the effect of Spirulina platensis protease hydrolyzate (SPPH) on the lipid metabolism and gut microbiota in high-fat diet (HFD)-fed rats. Our study showed that SPPH decreased the levels of triglyceride (TG), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), and aspartate transaminase (AST), but increased the level of high-density-lipoprotein cholesterol (HDL-c) in serum and liver. Moreover, SPPH had a hypolipidemic effect as indicated by the down-regulation of sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl CoA carboxylase (ACC), SREBP-1c, and peroxisome proliferator-activated receptor-γ (PPARγ) and the up-regulation of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptorα (PPARα) at the mRNA level in liver. SPPH treatment enriched the abundance of beneficial bacteria. In conclusion, our study showed that SPPH might be produce glucose metabolic benefits in rats with diet-induced LMD. The mechanisms underlying the beneficial effects of SPPH on the metabolism remain to be further investigated. Collectively, the above-mentioned findings illustrate that Spirulina platensis peptides have the potential to ameliorate lipid metabolic disorders, and our data provides evidence that SPPH might be used as an adjuvant therapy and functional food in obese and diabetic individuals.

scholarly journals Regulation of microRNAs in high-fat diet induced hyperlipidemic hamsters

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Teodora Barbalata ◽  
◽  
Lu Zhang ◽  
Madalina D. Dulceanu ◽  
Camelia S. Stancu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Discrete Distribution ◽  
Functional Enrichment ◽  
High Fat ◽  
Fat Cell ◽  
Specific Distribution ◽  
Different Tissues

AbstractDyslipidemia is a documented risk factor for cardiovascular diseases and other metabolic disorders. Therefore, the analysis of hyperlipidemia (HL)-related miRNAs is a potential approach for achieving new prognostic markers in lipid-metabolism related diseases. We aimed to analyze specific distribution of miRNAs in different tissues from HL animals. Golden Syrian hamsters were fed either regular chow (NL) or high-fat diet (HL) for 12 weeks. Microarray miRNAs profiling was performed in liver, heart and small intestine and data analyzed by R-studio software. Functional enrichment bioinformatics analysis was performed using miRWalk and DAVID tools. We observed a dysregulation of miRNAs in HL tissues evidencing a discrete distribution in the heart-liver axis and three lipid metabolism-related miRNAs were identified: hsa-miR-223-3p, hsa-miR-21-5p, and hsa-miR-146a-5p. Expression levels of these miRNAs were increased in HL livers and hearts. Functional bioinformatics analysis showed involvement of these miRNAs in the regulation of biological processes altered in HL conditions such as lipid metabolic process, fat cell differentiation, regulation of smooth muscle cells and cardiac septum development. We identified a set of miRNAs dysregulated in different tissues of HFD-induced HL hamsters. These findings motivate further studies aiming to investigate novel molecular mechanisms of lipid metabolism and atherogenic HL.

scholarly journals Sijunzi, Lizhong, and Fuzilizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease through Activation of PPAR Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiayao Yang ◽  
Dongqing Tao ◽  
Wei Ma ◽  
Song Liu ◽  
Yan Liao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal

Objective. Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD). Methods. Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD and were thereafter administered Sijunzi (8 g/kg/d), Lizhong (10 g/kg/d), or Fuzilizhong (10 g/kg/d) by gavage for four weeks. Hepatic damage, lipid accumulation, inflammation, autophagy, and peroxisome proliferator-activated receptor-α signaling were evaluated. Results. The high-fat diet-fed rats showed typical symptoms of NAFLD, including elevated levels of hepatic damage indicators, increased hepatic lipid deposition and fibrosis, severe liver inflammation, and prominent autophagy. Upon administration of Sijunzi, Lizhong, and Fuzilizhong, liver health was improved remarkably, along with ameliorated symptoms of NAFLD. In addition, NAFLD-suppressed peroxisome proliferator-activated receptor-α signaling was reactivated after treatment with the three types of decoctions. Conclusions. The results collectively signify the effective therapeutic and protective functions of Sijunzi, Lizhong, and Fuzilizhong against NAFLD and demonstrate the potential of Chinese herbal medication in mitigating the symptoms of liver diseases. Novelty of the Work. Traditional Chinese herbal medicine has been used for centuries to treat various diseases, but the molecular mechanisms of individual ingredients have rarely been studied. The novelty of our work lies in elucidating the specific signaling pathways involved in the control of NAFLD using three common Chinese herbal decoctions. We suggest that natural herbal formulations can be effective therapeutic agents to combat against NAFLD.

Effects of Zinc Alpha2 Glycoprotein on Lipid Metabolism of Liver in High-Fat Diet-Induced Obese Mice

2017 ◽  
Vol 49 (10) ◽  
pp. 793-800 ◽  
Author(s):  
Guoqiang Fan ◽  
Yu Qiao ◽  
Shixing Gao ◽  
Jun Guo ◽  
Ruqian Zhao ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Recombinant Plasmid ◽  
Diet Group ◽  
Normal Diet ◽  
Hormone Sensitive Lipase ◽  
High Fat ◽  
Hepatic Lipid ◽  
Protein Levels

AbstractZinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.

scholarly journals Beta-Glucan-Rich Extract fromPleurotus sajor-caju(Fr.) Singer Prevents Obesity and Oxidative Stress in C57BL/6J Mice Fed on a High-Fat Diet

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
G. Kanagasabapathy ◽  
S. N. A. Malek ◽  
A. A. Mahmood ◽  
K. H. Chua ◽  
S. Vikineswary ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Lipid Hydroperoxide ◽  
Protein Carbonyl ◽  
Normal Diet ◽  
Hormone Sensitive Lipase ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Beta Glucan ◽  
Peroxisome Proliferator Activated Receptor

Mushrooms have been used in folk medicine for thousands of years. In this study, the effect ofβ-glucan-rich extract ofP. sajor-caju(GE) on lipid lowering and antioxidant potential was assessed in C57BL/6J mice fed on a high-fat diet. Obesity was induced in C57BL/6J mice by feeding a high-fat diet. The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120, and HFD240 (for high-fat diet), where the mice were administrated with three dosages of GE (60, 120, and 240 mg GE/kg b.w). Metformin (2 mg/kg b.w) served as positive control. GE-treated groups showed significantly reduced body weight, serum lipid, and liver enzymes levels. GE also attenuated protein carbonyl and lipid hydroperoxide levels by increasing the enzymic antioxidants (SOD, CAT, and GPx) activities in the mice. GE-treated groups induced the expression of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) while downregulated the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory binding protein-1c (SREBP-1c), and lipoprotein lipase (LPL). Hence, GE prevented weight gain in the mice by inducing lipolysis and may be valuable in the formulation of adjuvant therapy for obesity.

scholarly journals Mouse Abdominal Fat Depots Reduced by Butyric Acid-Producing Leuconostoc mesenteroides

2020 ◽  
Vol 8 (8) ◽  
pp. 1180 ◽  
Author(s):  
John Jackson Yang ◽  
Minh Tan Pham ◽  
Adelia Riezka Rahim ◽  
Tsung-Hsien Chuang ◽  
Ming-Fa Hsieh ◽  
...  
Keyword(s):  
Butyric Acid ◽  
High Fat Diet ◽  
Lipid Droplets ◽  
Leuconostoc Mesenteroides ◽  
Abdominal Fat ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Fat Depots ◽  
Ppar Γ ◽  
Free Fatty Acid Receptor

The activation of peroxisome proliferator-activated rece ptor gamma (PPAR-γ) is known to induce the differentiation of adipocytes. This study aimed to investigate the probiotic effect of Leuconostoc mesenteroides (L. mesenteroides) on high-fat diet (HFD)-induced PPAR-γ activation and abdominal fat depots. Incubation of differentiated 3T3-L1 adipocytes with media of L. mesenteroides EH-1, a butyric acid-producing strain, significantly reduced the amounts of lipid droplets. The oral administration of L. mesenteroides EH-1 produced large amounts (>1 mM) of butyric acid in cecum and attenuated the HFD-induced upregulation of PPAR-γ and accumulation of abdominal fats in mice. The combination of 2% glucose with L. mesenteroides EH-1 increased the production of butyric acid and potentiated the probiotic activity of L. mesenteroides EH-1 against the formation of lipid droplets in 3T3-L1 adipocytes as well as abdominal fats in HFD-fed mice. The inhibition of free fatty acid receptor 2 (Ffar2) by its antagonist, GLPG-0974, markedly diminished the probiotic effects of L. mesenteroides EH-1 plus glucose on the suppression of HFD-induced PPAR-γ and abdominal fats. Besides demonstrating the probiotic value of L. mesenteroides EH-1, our results highlight the possible therapy targeting the butyric acid-activated Ffar2 pathway to reduce abdominal fats.

High-Fat Diet-Induced Obesity Aggravates Food Allergy by Intestinal Barrier Destruction and Inflammation

2021 ◽  
pp. 1-13
Author(s):  
Yanjun Gu ◽  
Xiaoya Guo ◽  
Shanfeng Sun ◽  
Huilian Che
Keyword(s):  
Food Allergy ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Intestinal Barrier ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Ppar Γ

<b><i>Introduction:</i></b> The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. <b><i>Methods:</i></b> Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). <b><i>Results:</i></b> In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. <b><i>Conclusions:</i></b> Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.

scholarly journals Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m6A RNA Methylation

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiamin Wu ◽  
Yi Li ◽  
Jiayao Yu ◽  
Zhending Gan ◽  
Wenyao Wei ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Peroxisome Proliferator ◽  
Domain Family ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rna Methylation ◽  
Low Fat Diet ◽  
Mrna Methylation ◽  
Yth Domain

Purpose:N6-methyladenosine (m6A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m6A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m6A RNA methylation in the liver of mice.Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m6A modification in the liver were assessed.Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m6A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice.

scholarly journals Network Modeling and Inference of Peroxisome Proliferator-Activated Receptor Pathway in High fat diet-linked Obesity

2020 ◽  
Author(s):  
Haswanth Vundavilli ◽  
Lokesh P. Tripathi ◽  
Aniruddha Datta ◽  
Kenji Mizuguchi
Keyword(s):  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Health Concern ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Modeling Tools ◽  
Peroxisome Proliferator Activated Receptor

AbstractSystems biology aims to understand how holistic systems theory can be used to explain the observable living system characteristics, and mathematical modeling tools have been successful in understanding the intricate relationships underlying cellular functions. Lately, researchers have been interested in understanding molecular mechanisms underlying obesity, which is a major health concern worldwide and has been linked to several diseases. Various mechanisms such as peroxisome proliferator-activated receptors (PPARs) are known to modulate obesity-induced inflammation and its consequences. In this study, we have modeled the PPAR pathway using a Bayesian model and inferred the sub-pathways that are potentially responsible for the activation of the output processes that are associated with high fat diet (HFD)-induced obesity. We examined a previously published dataset from a study that compared gene expression profiles of 40 mice maintained on HFD against 40 mice fed with chow diet (CD). Our simulations have highlighted that GPCR and FATCD36 sub-pathways were aberrantly active in HFD mice and are therefore favorable targets for anti-obesity strategies. We further cross-validated our observations with experimental results from the literature. We believe that mathematical models such as those presented in the present study can help in inferring other pathways and deducing significant biological relationships.

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