Role of mTOR in Glucose and Lipid Metabolism

Mao, Zhuo; Zhang, Weizhen

doi:10.3390/ijms19072043

Cited by 202 publications

(209 citation statements)

References 97 publications

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“…For instance, excessive mTORC1 activity enhances lipogenesis by the induction of Sterol regulatory element-binding protein 1 (SREBP1c) [9][10][11][12]. Furthermore, mTORC1 activation suppresses peroxisome proliferator-activated receptor α (PPARα) activity, which in turn inhibits β-oxidation in the liver [13,14]. mTORC1 has been shown to suppress the autophagy pathway via regulation of autophagy activation kinase 1 (ULK1) [15,16].…”

Section: Introductionmentioning

confidence: 99%

Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

et al. 2019

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The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD.

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Section: Introductionmentioning

confidence: 99%

Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

et al. 2019

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“…Studies have shown that many obese patients with disordered lipid metabolism have dysfunction of mTOR in the body, suggesting that mTOR is involved in lipid metabolism [49][50][51]. Studies have shown that mTOR can increase the expression of SREBPs in fat synthesis-related genes and promote the splicing modification of SREBPs in Golgi apparatus.…”

Section: Discussionmentioning

confidence: 99%

Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway

Tang

et al. 2020

Journal of Diabetes Research

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Purpose. To investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics and find new therapeutic basis on obese type 2 diabetes mellitus (T2DM) patients. Materials and Methods. Thirty-two rats were divided into nondiabetic group, diabetic group, sham group, and RYGB group. The Dual-energy X-ray absorptiometry (DEXA) was used to detect short-term curriculum vitae for rat body component and fat and lean mass. Hepatic lipid content and triglyceride levels were detected by Oil Red O staining. Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. The carbon dioxide production from the oxidation of [14C] oleate was measured. Plasma glucose was measured by glucose oxidase assay. The insulin and C-peptide were detected. Triacylglyceride (TG) and free fat acid (FFA) in plasma were determined by enzymatic colorimetric assays. Results. RYGB improved metabolic parameters and enhanced plasma GLP-1 level, ameliorated the lipopexia, and increased insulin sensitivity in the liver; RYGB promoted the hepatic autophagy and inhibited the mTOR/p70S6K signaling pathway. GLP-1 reduced fat load and increased fatty acid β-oxidation by activated autophagy to regulate the hepatic lipid pathway through mTOR/p70S6K signaling pathway. Conclusions. RYGB may reduce liver lipid toxicity and improve insulin sensitivity through activating the hepatic fat hydrolysis pathway and inhibiting the liver fat synthesis pathway. However, the transport pathway of liver fat does not play a key role.

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“…Type 2 diabetes. The roles of mTOR in glucose and lipid metabolism and diabetes have been extensively studied (57,58). Type 2 diabetes can be successfully induced in zebrafish by a daily high fat diet consisting of brine shrimp and 1% egg yolk for 10 weeks.…”

Section: The Role Of Ztor In Age-related Diseases In the Zebrafish Modelmentioning

confidence: 99%

Understanding the Role of ztor in Aging-related Diseases Using the Zebrafish Model

Khor

Noor

Wong

2019

In Vivo

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The mammalian target of rapamycin (mTOR), a 289 kDa serine/threonine protein kinase of the phosphoinositide 3-kinase (PI3K)-related family is known for its role in regulating lifespan and the aging process in humans and rodents. Aging in zebrafish very much resembles aging in humans. Aged zebrafish often manifest with spinal curvature, cataracts and cognitive frailty, akin to human age-related phenotypical effects such as osteoarthritis, dwindling vision and cognitive dysfunction. However, the role of the zebrafish orthologue of mTOR, ztor, is less defined in these areas. This review paper discusses the tale of growing old in the zebrafish, the physiological roles of ztor in normal developmental processes and its involvement in the pathogenesis of aging-related diseases such as metabolic disorders and cancers.

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Role of mTOR in Glucose and Lipid Metabolism

Cited by 202 publications

References 97 publications

Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway

Understanding the Role of ztor in Aging-related Diseases Using the Zebrafish Model

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