Egusquiza, R. J. | bioRxiv Science

bioRxiv2025

The effect of cold exposure on energy expenditure of mice fed an obesogenic diet

ObjectiveCold exposure is one of the most powerful physiological stimuli for thermogenic adipose tissue activity and may positively impact metabolic homeostasis. An important gap in knowledge is whether mice with diet-induced obesity respond to cold similarly to their lean counterparts. The goal of the present study was to compare the response to cold exposure between mice fed a standard (normal-fat) diet and a higher-fat diet. MethodsMale C56BL/6J mice fed a standard diet (13.1% fat) or a higher-fat diet (21.6% fat) during adulthood and exposed to cold (4-6{degrees}C) following different approaches. Body weight, body composition, food intake, rectal temperature, energy expenditure, and respiratory exchange ratio were assessed. ResultsCold exposure significantly increased energy expenditure and limited weight gain despite elevated food intake in mice fed either a standard or a higher-fat diet, while body composition, body temperature, and respiratory exchange ratio remained stable across both dietary groups. Moreover, energy expenditure measured at 4-6 {degrees}C was comparable between mice fed standard and higher-fat diets, demonstrating that cold-induced thermogenesis may elicit a consistent metabolic response independent of dietary fat content. ConclusionsOur results demonstrated that cold exposure increased energy expenditure in both lean and obese animals, highlighting thermogenesis as a promising target for obesity treatment beyond current approaches focusing on appetite suppression. HighlightsO_LICold exposure increases energy expenditure and limits weight gain in both control diet and higher-fat diet-fed mice, despite increased food intake. C_LIO_LICore body temperature and body composition remain stable during cold exposure, regardless of dietary fat content. C_LIO_LICold-induced thermogenesis elicits a comparable metabolic response in control diet and higher-fat diet-fed mice, supporting its potential as a therapeutic strategy for obesity. C_LI

physiology↗

bioRxiv2022

Heritable changes in chromatin contacts linked to transgenerational obesity

Burgeoning evidence demonstrates that responses to environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations1,2. This is controversial because underlying mechanisms remain to be identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology. Here, we used an established murine model of transgenerational obesity to show that direct or ancestral exposure to the obesogen tributyltin (TBT) elicited persistent changes in topologically associating domains (TADs) in primordial germ cells (PGCs) isolated from embryos of exposed and subsequent unexposed generations. New TAD boundaries were formed within the Ide gene encoding insulin degrading enzyme in the exposed PGCs, then stably maintained in PGCs of the subsequent (unexposed) two generations. Concomitantly, Ide mRNA expression was decreased in livers of male descendants from the exposed dams. These animals were hyperinsulinemic and hyperglycemic, phenocopying Ide-deficient mice that are predisposed to adult-onset obesity. Creation of new TAD boundaries in PGCs, suppression of hepatic Ide mRNA, increased fat mass, hyperinsulinemia and hyperglycemia were male-specific. Our results provide a plausible molecular mechanism underlying transmission of the transgenerational predisposition to obesity caused by gestational exposure to an environmental obesogen. They also provide an entry point for future studies aimed at understanding how environmental exposures alter chromatin structure to influence physiology across multiple generations in mammals.

developmental biology↗