The role of suppression of hepatic SCD1 expression in the metabolic effects of dietary methionine restriction

Dietary methionine restriction (MR) produces concurrent increases in energy intake and expenditure, but the proportionately larger increase in energy expenditure (EE) effectively limits weight gain and adipose tissue accretion over time. Increased hepatic FGF21 is essential to MR-dependent increases in EE, but it is unknown whether the downregulation of hepatic stearoyl-CoA desaturase-1 (SCD1) by MR could also be a contributing factor. Global deletion of SCD1 mimics cold exposure in mice housed at 23째C by compromising the insular properties of the skin. The resulting cold stress increases EE, limits fat deposition, reduces hepatic lipids, and increases insulin sensitivity by activating thermoregulatory thermogenesis. To examine the efficacy of MR in the absence of SCD1 and without cold stress, the biological efficacy of MR in Scd1-/- mice housed near thermoneutrality (28째C) was evaluated. Compared to wild type (WT) mice on the control diet, Scd1-/- mice were leaner, had higher EE, lower hepatic and serum triglycerides, and lower serum leptin and insulin. Although dietary MR increased adipose tissue UCP1 expression, hepatic Fgf21 mRNA, 24 h EE, and reduced serum triglycerides in Scd1-/- mice, it failed to reduce adiposity or produce any further reduction in hepatic triglycerides, serum insulin, or serum leptin. These findings indicate that even when thermal stress is minimized, global deletion of SCD1 mimics and effectively masks many of the metabolic responses to dietary MR. However, the retention of several key effects of dietary MR in this model indicates that SCD1 is not a mediator of the biological effects of the diet.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author