Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females.

Autor:	Szalanczy AM; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States., Goff E; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States., Seshie O; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States., Deal A; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States., Grzybowski M; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States., Klotz J; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States., Chuang Key CC; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States., Geurts AM; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States., Solberg Woods LC; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Sep 21; Vol. 13, pp. 942574. Date of Electronic Publication: 2022 Sep 21 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.942574
Abstrakt:	Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity through a genome-wide association study in outbred rats, where increased liver expression of Krtcap3 correlated with decreased fat mass. Here we seek to confirm that Krtcap3 expression affects adiposity traits. To do so, we developed an in vivo whole-body Krtcap3 knock-out (KO) rat model. Wild-type (WT) and KO rats were placed onto a high-fat (HFD) or low-fat diet (LFD) at 6 weeks of age and were maintained on diet for 13 weeks, followed by assessments of metabolic health. We hypothesized that Krtcap3 -KO rats will have increased adiposity and a worsened metabolic phenotype relative to WT. We found that KO male and female rats have significantly increased body weight versus WT, with the largest effect in females on a HFD. KO females also ate more and had greater adiposity, but were more insulin sensitive than WT regardless of diet condition. Although KO males weighed more than WT under both diet conditions, there were no differences in eating behavior or fat mass. Interestingly, KO males on a HFD were more insulin resistant than WT. This study confirms that Krtcap3 plays a role in body weight regulation and demonstrates genotype- and sex-specific effects on food intake, adiposity, and insulin sensitivity. Future studies will seek to better understand these sex differences, the role of diet, and establish a mechanism for Krtcap3 in obesity. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Szalanczy, Goff, Seshie, Deal, Grzybowski, Klotz, Chuang Key, Geurts and Solberg Woods.)
Databáze:	MEDLINE
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