Emodin Protects against High-Fat Diet-Induced Obesity via Regulation of AMP-Activated Protein Kinase Pathways in White Adipose Tissue

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.

Download Full-text

Dietary Silk Peptide Prevents High-Fat Diet-Induced Obesity and Promotes Adipose Browning by Activating AMP-Activated Protein Kinase in Mice

Nutrients ◽

10.3390/nu12010201 ◽

2020 ◽

Vol 12 (1) ◽

pp. 201 ◽

Cited By ~ 5

Author(s):

Kippeum Lee ◽

Heegu Jin ◽

Sungwoo Chei ◽

Jeong-Yong Lee ◽

Hyun-Ji Oh ◽

...

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

High Fat Diet ◽

Ex Vivo ◽

Uncoupling Protein ◽

Acid Oxidation ◽

High Fat ◽

Diet Induced Obesity ◽

Silk Peptide ◽

Amp Activated Protein Kinase

Obesity is associated with metabolic syndrome and other chronic diseases, and is caused when the energy intake is greater than the energy expenditure. We aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet-induced obesity, and whether it induces browning and fatty acid oxidation (FAO) in white adipose tissue (WAT), using in vivo and ex vivo approaches. We determined the effects of dietary SP in high-fat diet-fed obese mice. The expression of adipose tissue-specific genes was quantified by western blotting, qRT-PCR, and immunofluorescence analysis. We also investigated whether SP directly induces browning in primarily subcutaneous WAT-derived adipocytes. Our findings demonstrate that SP has a browning effect in WAT by upregulating AMP-activated Protein Kinase (AMPK) phosphorylation and uncoupling protein 1 (UCP1) expression. SP also suppresses adipogenesis and promotes FAO, implying that it may have potential as an anti-obesity drug.

Download Full-text

Viola mandshurica ethanolic extract prevents high-fat-diet-induced obesity in mice by activating AMP-activated protein kinase

Environmental Toxicology and Pharmacology ◽

10.1016/j.etap.2014.04.028 ◽

2014 ◽

Vol 38 (1) ◽

pp. 41-50 ◽

Cited By ~ 10

Author(s):

Yoon-Young Sung ◽

Dong-Seon Kim ◽

Ho Kyoung Kim

Keyword(s):

Protein Kinase ◽

High Fat Diet ◽

Ethanolic Extract ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity In Mice ◽

Amp Activated Protein Kinase

Download Full-text

Insulin receptor substrate‐1 inhibits high‐fat diet‐induced obesity by browning of white adipose tissue through miR‐503

The FASEB Journal ◽

10.1096/fj.201903283rr ◽

2020 ◽

Vol 34 (9) ◽

pp. 12308-12323

Author(s):

Xiao‐Fei Man ◽

Nan Hu ◽

Shu‐Wen Tan ◽

Hao‐Neng Tang ◽

Yue Guo ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Receptor ◽

White Adipose Tissue ◽

High Fat Diet ◽

Insulin Receptor Substrate ◽

High Fat ◽

Insulin Receptor Substrate 1 ◽

Diet Induced Obesity

Download Full-text

A High-Fat Diet Attenuates Amp-Activated Protein Kinase α1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development in Vivo

10.2337/figshare.13259768 ◽

2020 ◽

Author(s):

Ada Admin ◽

Chenghui Yan ◽

Xiaoxiang Tian ◽

Jiayin Li ◽

Dan Liu ◽

...

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Fatty Liver ◽

Lipid Accumulation ◽

High Fat Diet ◽

Liver Development ◽

High Fat ◽

Tissue Specific ◽

Nonalcoholic Fatty Liver ◽

Amp Activated Protein Kinase

Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (<a>AT</a>) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (<a>NAFLD</a>). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a <a>high-fat diet </a>(<a>HFD</a>) or treated with metformin- or GW4869 and with AMP-activated protein kinase (AMPKα1) floxed (Prkaα1fl/fl/WT), <a>Prkaα1-/-</a>, liver tissue-specific Prkaα1-/-, or AT-specific Prkaα1-/- modification. In cultured adipocytes and white adipose tissue (WAT), the absence of <a>AMPKα1</a> increased exosome release and exosomal proteins by elevating <a>tumor susceptibility gene 101 (TSG101</a>)-mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death in <a>Prkaα1-/- </a>and adipose tissue-specific Prkaα1-/- mice than in WT and liver-specific Prkaα1-/- mice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specific Prkaα1-/- mice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers in Prkaα1-/- and adipocyte-specific Prkaα1-/- mice. We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT C<a>D36</a>-containing exosomes.

Download Full-text