Session: OR30-Central Regulation of Appetite & Feeding
Room 304 (Moscone Center)
[Animals and methods] To generate brain-specific NPR-B deficient mice, we crossed mutant mice carrying the floxed NPR-B gene with transgenic mice expressing Cre recombinase under the control of the rat nestin promoter. In this study, 8-week-old male mice were given free access to water and either standard diet (SD) (F-2; 12 % calories from fat) or high-fat diet (HFD) (D12492; 60 % calories from fat). At 16 weeks of age, the animals were sacrificed for further analysis.
[Results] There was no difference in naso-anal length, food intake, or oxygen consumption between NPR-B deficient mice and control mice on either a SD or a HFD. Body weight of NPR-B deficient mice fed a SD was significantly lower than control mice from 11 weeks of age. When fed a HFD, brain NPR-B deficient mice were resistant to weight gain. At 16 weeks of age, NPR-B deficient mice fed a HFD were 13% less in body weight than control mice. And, the weight of the liver and the mesenteric adipose tissue were significantly decreased in NPR-B deficient mice fed a HFD compared with control mice. In addition, NPR-B deficient mice fed a HFD exhibited significantly decreased hepatic triglyceride and cholesterol contents, and fatty acid translocase (also known as CD36) mRNA expression in the liver compared with control mice. These changes were accompanied by significantly decreased plasma insulin and FFA levels in NPR-B deficient mice fed a HFD compared with control mice. In the mesenteric adipose tissue, the expression of UCP2 mRNA was significantly decreased in NPR-B deficient mice fed a HFD compared with control mice. Furthermore, in the hypothalamus, NPR-B deficient mice fed a HFD showed significantly increased POMC mRNA and CART mRNA expression compared with control mice.
[Conclusions] In this study, we demonstrated that brain NPR-B deficiency prevented high-fat diet-induced fat accumulation in the liver and the visceral adipose tissue, which might be accompanied by improvement of systemic insulin sensitivity. Our findings suggest that CNP/NPR-B signaling in the brain could be a new central factor that regulate peripheral lipid metabolism.
Nothing to Disclose: YY, NY, GK, YO, YM, II, HA, NK, MM, AY, HA, KO, RK, KN
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