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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 291 - 303 (13page)
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초록· 키워드
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Objective Ceramide is a signaling molecule that contributes to insulin resistance and hepatosteatosis. In the present study, we activated de novo ceramide synthesis by inducing the hepatic expression of Sptlc2 to investigate the role of ceramide in glucose and lipid metabolism. Methods We first constructed an adenovirus containing Sptlc2 (AdSptlc2), which encodes a major catalytic subunit of serine palmitoyltransferase (SPT). We then infected hepatocytes and mice fed a regular diet with AdSptlc2 to activate de novo ceramide biosynthesis. The liver-specific effects of ceramide biosynthesis on glucose and lipid metabolism were investigated by measuring changes in insulin signaling, lipid droplet formation, and very low-density lipoprotein (VLDL) secretion. Results In HepG2 hepatocytes, adenoviral Sptlc2 expression inhibited insulin signaling and increased ceramide levels via activation of c-Jun N-terminal kinase and serine phosphorylation of insulin receptor substrate 1. In contrast, in mice, AdSptlc2 infection decreased plasma glucose levels by downregulating gluconeogenic genes and increased plasma triglyceride levels by increasing VLDL secretion. In mice infected with AdSptlc2, glucose intolerance and insulin sensitivity improved, while pyruvate utilization via gluconeogenesis decreased. Conclusion Hepatic ceramide was found to modulate hepatosteatosis and the insulin response via increased VLDL secretion and inhibition of gluconeogenesis in vivo. Although inhibition of the insulin response was observed in vitro, the compensatory mechanism of relieving ceramide-induced stress and reducing ceramide levels resulted in improvements of glucose and lipid metabolic profiles in vivo. This discrepancy between in vitro and in vivo regulation mechanisms suggests that ceramide plays a role in non-alcoholic fatty liver disease and insulin resistance.
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등록된 정보가 없습니다.
참고문헌 (35)
참고문헌 신청
Barr EL / 2010 / HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population : the Australian Diabetes, Obesity and Lifestyle Study(AusDiab)study / Diabetologia 53:79~88
Hastie CE / 2010 / Obesity paradox in a cohort of 4880 consecutive patients undergoing percutaneous coronary intervention / Eur Heart J 31:222~226
Roberts AW / 2009 / Review article : left ventricular dysfunction and heart failure in metabolic syndrome and diabetes without overt coronary artery disease--do we need to screen our patients? / Diab Vasc Dis Res 6:153~163
Bradbury MW / 2006 / Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake : possible role in steatosis / Am J Physiol Gastrointest Liver Physiol 290:G194~G198
Unger RH / 2003 / Lipid overload and overflow : metabolic trauma and the metabolic syndrome / Trends Endocrinol Metab 14:398~403
Hastie CE / 2010 / Obesity paradox in a cohort of 4880 consecutive patients undergoing percutaneous coronary intervention / Eur Heart J 31:222~226
Roberts AW / 2009 / Review article : left ventricular dysfunction and heart failure in metabolic syndrome and diabetes without overt coronary artery disease--do we need to screen our patients? / Diab Vasc Dis Res 6:153~163
Bradbury MW / 2006 / Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake : possible role in steatosis / Am J Physiol Gastrointest Liver Physiol 290:G194~G198
Unger RH / 2003 / Lipid overload and overflow : metabolic trauma and the metabolic syndrome / Trends Endocrinol Metab 14:398~403
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