Impact of housing temperature on adipose tissue HDAC9 expression and adipogenic differentiation in high fat‐fed mice

Abstract

ObjectiveImpaired adipogenic differentiation exacerbates metabolic disease in obesity. This study reported that high‐fat diet (HFD)‐fed mice housed at thermoneutrality exhibited impaired adipogenic differentiation, attributed to increased expression of histone deacetylase 9 (HDAC9). However, the impact of HFD on adipogenic differentiation is reportedly variable, possibly reflecting divergent environmental conditions such as housing temperature.MethodsC57BL/6J (wild‐type [WT]) mice were housed at either thermoneutral (28–30°C) or ambient (20–22°C) temperature and fed HFD or chow diet (CD) for 12 weeks. For acute exposure experiments, WT or transient receptor potential cation channel subfamily M member 8 (TRPM8) knockout mice housed under thermoneutrality were acutely exposed to ambient temperature for 6 to 24 h.ResultsWT mice fed HFD and housed at thermoneutrality, compared with ambient temperature, gained more weight despite reduced food intake. They likewise exhibited increased inguinal adipose tissue HDAC9 expression and reduced adipogenic differentiation in vitro and in vivo compared with CD‐fed mice. Conversely, HFD‐fed mice housed at ambient temperature exhibited minimal change in adipose HDAC9 expression or adipogenic differentiation. Acute exposure of WT mice to ambient temperature reduced adipose HDAC9 expression independent of sympathetic β‐adrenergic signaling via a TRPM8‐dependent mechanism.ConclusionsAdipose HDAC9 expression is temperature sensitive, regulating adipogenic differentiation in HFD‐fed mice housed under thermoneutrality.

Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice

“…Like other class 2a HDACs, HDAC9 exhibits weak deacetylase activity, and its enzymatic domain is dispensable for regulation of adipogenic differentiation [10]. Interestingly, we observed impaired adipogenic differentiation, and increased Hdac9 expression, in inguinal adipose tissues of mice fed a high fat diet and housed at thermoneutral temperatures [19]. Under these conditions, deletion of Hdac9 resulted in increased energy expenditure and heat generation, in conjunction with browning of inguinal adipose tissues, which likely contributed to the favorable metabolic phenotype.…”

“…Additionally, our study was conducted in an ambient temperature environment. It is possible that Hdac9 overexpression could have a lesser impact under thermoneutral conditions, where endogenous Hdac9 expression in adipose tissues is upregulated [19]. Finally, in this study, mice were fed a standard laboratory diet and were therefore lean, so our findings cannot be extrapolated to murine models of obesity.…”

“…In contrast, housing mice at ambient temperature while feeding a high fat diet resulted in improved metabolic health, along with minimal changes in adipose Hdac9 expression and adipogenic differentiation. Short-term studies have indicated that inguinal adipose Hdac9 expression is sensitive to changes in housing temperature via a TRPM8dependent mechanism [19]. Thus, HDAC9 may function as a metabolic switch in adipose tissues, regulating the balance between energy storage and heat production to maintain homeostasis depending on environmental conditions [19].…”

“…Short-term studies have indicated that inguinal adipose Hdac9 expression is sensitive to changes in housing temperature via a TRPM8dependent mechanism [19]. Thus, HDAC9 may function as a metabolic switch in adipose tissues, regulating the balance between energy storage and heat production to maintain homeostasis depending on environmental conditions [19].…”