ABSTRACT: Obesity is a global health problem, which is characterized by the excessive fat accumulation or adiposity in the body and associated with other chronic metabolic disorders. Excess energy induces adipogenesis and lipid accumulation inside the existing adipocytes during obesity, which involves transcriptional changes and regulation. Recently, long non-coding RNAs (lncRNAs) have been implicated in regulation of adipogenesis and adipose tissue function. Mouse lncRNA U90926 was previously identified as a repressor of in vitro adipogenesis in 3T3-L1 preadipocytes. Based on this, we hypothesized that U90926 may repress weight gain and adiposity in vivo. To test the hypothesis, we leveraged U90926-deficient (U9-KO) mice, which we recently generated, with a generalized high-throughput phenotyping pipeline and focused follow-up phenotyping experiments. Compared with WT, U9-KO mice showed no major differences across a wide range of behavioral, neurological, and other physiological parameters. In mice fed a standard diet, we have found no differences in obesity-related phenotypes such as weight gain, fat mass accumulation, and plasma concentration of glucose, insulin, triglycerides, and free fatty acids in U9-KO mice in comparison with WT. U90926 deficiency did not have a major effect on perigonadal white adipose tissue morphology and gene expression profile. Furthermore, in mice fed a high fat diet, we found increased expression of U90926, yet no effect of U90926 deficiency on weight gain, fat mass, adipogenesis marker expression, and immune cell infiltration into the adipose tissue. Taken together, these data suggest that the lncRNA U90926 lacks an essential role in obesity-related phenotypes as well as adipocyte biology in vivo.
