Tpcn2 Knock‐Out Mice Have Improved Insulin Sensitivity and Are Protected Against High‐Fat Diet Induced Weight Gain.

作者：Leah Solberg Woods; Katie Holl; Hong He; Sarah DeBehnke; Chay Teng Yeo; Polly Hansen; Abraham Gebre; Sandra Leone‐Kabler; Margarida Ruas; John Parks; John Parrington

来源：The FASEB Journal, 2018, 32(S1).

DOI：10.1096/fasebj.2018.32.1_supplement.754.4

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two‐pore channel 2 ( Tpcn2 ) knock‐out mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared to wild type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knock‐out mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knock‐out (KO), heterozygous (Het) and wild‐type (WT) mice were fed a low fat (LF) or high fat (HF) diet for 24 weeks. HF diet significantly increases body weight in WT mice relative to those on the LF diet, whereas HF diet consumption does not significantly affect body weight in Het or KO mice. We confirm that male KO mice have improved insulin sensitivity relative to WT mice. Unfortunately, because HF diet does not lead to insulin resistance in any of the mice, we are unable to claim a direct relationship between diet‐induced protection from insulin resistance and weight gain in the KO mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet‐fed mice where there is increased cholesterol and triglycerides across all genotypes. Fasting glucose, insulin and glucose tolerance levels do not differ by genotype or diet in male mice. In contrast, females consuming the HF diet exhibit glucose intolerance and hyperinsulinemia relative to females on the LF diet, but these effects are independent of genotype. These data demonstrate that male KO mice have improved insulin sensitivity and both male and female KO mice are protected against diet‐induced weight gain independent from changes in glucose tolerance or lipid levels.(#br)Support or Funding Information(#br)by R01 DK088975, R01 DK106386, Department of Pediatrics at the Medical College of Wisconsin(#br)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .