Effects of low-fat diet and aging on metabolic profiles of Creb3l4 knockout mice

Background/Objectives: Increased adipose tissue mass closely associates with the development of insulin resistance and type 2 diabetes mellitus. Previously, we reported that CREB3L4 expressed in adipose tissue negatively regulates adipogenesis, and Creb3l4 knockout mice fed a high-fat diet for 16 weeks showed fat cell hyperplasia, with improved glucose tolerance and insulin sensitivity. These mice did not show significant weight gain and fat mass. Because fat diet or aging is known to be associated with the development of obesity, we examined the effects of Creb3l4 gene subjected to low-fat diet (LFD) or aging process on body composition and obesity risk. Subjects/Methods: We fed Creb3l4 knockout mice a low-fat diet for 16 weeks (LFD group) or chow diet for over 1 year (aged group) and observed various metabolic parameters in the LFD-fed and aged Creb3l4 knockout mice. Results: LFD-fed and aged Creb3l4 knockout mice showed significant weight gain and adiposity, impaired glucose tolerance and decreased insulin sensitivity, compared with wild-type mice. Conclusions: Creb3l4 has a critical role in metabolic phenotypes and a better understanding of its function may provide improved insight into the etiology of diabetes and other metabolic disorders.