Article

Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
The Journal of Lipid Research (Impact Factor: 4.73). 11/2006; 47(10):2280-90. DOI: 10.1194/jlr.M600198-JLR200
Source: PubMed

ABSTRACT Lipogenic diets that are completely devoid of methionine and choline (MCD) induce hepatic steatosis. MCD feeding also provokes systemic weight loss, for unclear reasons. In this study, we found that MCD feeding causes profound hepatic suppression of the gene encoding stearoyl-coenzyme A desaturase-1 (SCD-1), an enzyme whose regulation has significant effects on metabolic rate. Within 7 days of MCD exposure, hepatic SCD-1 mRNA decreased to nearly undetectable levels. By day 21, SCD-1 protein was absent from hepatic microsomes and fatty acids showed a decrease in monounsaturated species. These changes in hepatic SCD-1 were accompanied by signs of hypermetabolism. Calorimetry revealed that MCD-fed mice consumed 37% more energy than control mice (P = 0.0003). MCD feeding also stimulated fatty acid oxidation, although fatty oxidation genes were not significantly upregulated. Interestingly, despite their increased metabolic rate, MCD-fed mice did not increase their food consumption, and as a result, they lost 26% of their body weight in 21 days. In summary, MCD feeding suppresses SCD-1 in the liver, which likely contributes to hypermetabolism and weight loss. MCD feeding also induces hepatic steatosis, by an independent mechanism. Viewed together, these two disparate consequences of MCD feeding (weight loss and hepatic steatosis) give the appearance of an unusual form of lipodystrophy.

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Available from: Lorenzo Arnaboldi, Apr 16, 2015
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    • "In addition to the accumulation of hepatic triglycerides in response to choline deficiency and lipogenesis [22] [23], and impaired antioxidant defences in response to methionine deficiency , induction of CYP2E1 (or CYP4A) [24] and C/EBPb [17] may induce oxidative stress in the MCD model of steatohepatitis. "
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