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

item RIZKI, G
item YAN, J
item LEE, GS
item NG, RK
item PITAS, RE

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2006
Publication Date: 10/1/2006
Citation: Rizki, G., Arnaboldi, L., Gabrielli, B., Yan, J., Lee, G., Ng, R., Turner, S., Badger, T.M., Pitas, R., Maher, J.J. 2006. Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1. Journal of Lipid Research. 47(10):2280-2290.

Interpretive Summary: Fat storage in the liver (steatosis) is a normal process, but under certain circumstances leads to fatty liver disease. This is occurring with greater frequency in children as the obesity incidence increases at a younger age. Understanding the mechanisms by which this occurs may lead to a prevention strategy or treatment of these fat storage problems. This study found that one protein (an enzyme) important in fat metabolism may be a significant component in regulating metabolism key to either development of steatosis. Future work will determine how this information can be used to help prevent fat accumulation in children who consume diets that promote obesity.

Technical 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.