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Hepatic Stearoyl‐CoA Desaturase deficiency suppresses gluconeogenesis by regulating lipid profile of mitochondria
Author(s) -
Guo Changan,
Ntambi James M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.655.3
Subject(s) - medicine , endocrinology , insulin resistance , hyperinsulinemia , diabetes mellitus , metabolic syndrome , lipid metabolism , carbohydrate metabolism , hyperlipidemia , insulin , biology , polyunsaturated fatty acid , gluconeogenesis , oxidative stress , metabolism , chemistry , fatty acid , biochemistry
Obesity plays a central role in the metabolic syndrome, which includes hyperinsulinemia, hypertension, hyperlipidemia and an increased risk of atherosclerotic cardiovascular disease. A common health complication observed in obese patients is insulin resistance, a condition in which increased insulin levels are required to maintain normal blood glucose levels. Without proper intervention, the condition often deteriorates into type 2 diabetes mellitus, characterized by increased hepatic glucose production, and decreased glucose clearance by insulin‐responsive tissues. It has been suggested that high glucose is associated with increased oxidative stress, enhanced leukocyte‐endothelial interaction, and glycosylation of lipoproteins, apolipoproteins, and clotting factors. Identification of new therapeutic approaches to improve glycemic management via the inhibition of hepatic glucose production will be beneficial for diabetes, cardiovascular diseases and related metabolic disorders. Stearoyl‐CoA desaturase (SCD) expressed at high levels in several human tissues is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1), which are the major monounsaturated fatty acids of membrane phospholipids, triglycerides and cholesterol esters. Given the multiple roles of monounsaturated fatty acids, variation in stearoyl‐CoA desaturase activity in mammals would be expected to have a major effect on lipid metabolism. We and others have reported that global deletion of SCD1 in mice dramatically increases whole body energy expenditure and the loss of SCD1 activity in the liver suppresses hepatic glucose production when mice were fed a lipogenic diet. We hypothesize that the deficiency of SCD alters energy metabolism at the cellular level via the regulation of mitochondria function. Our preliminary data suggest that hepatic SCD1 deficiency alters the lipid profile of mitochondria membrane, therefore alters the membrane potential and metabolic rate of the cell. In addition, we show that the pharmaceutical inhibition of SCD activity reduces hepatic glucose production in the cell culture conditions. These studies provide essential information on the role of SCD on energy metabolism and, at the same time validate hepatic SCD enzymes as therapeutic targets against hyperglycemia in disease conditions, such as diabetes and metabolic syndrome. Support or Funding Information American Diabetes Association 7‐13‐BS‐118