Creatine Monohydrate Supplementation Increases White Adipose Tissue Mitochondrial Markers in Male and Female Rats in a Depot Specific Manner.

White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific stimuli. Non-shivering thermogenesis was previously thought to be uncoupling protein 1 (UCP1)-dependent however, recent evidence suggests that UCP1-independent mechanisms of thermogenesis exist. Namely, futile creatine cycling has been identified as a contributor to WAT thermogenesis. The purpose of this study was to examine the efficacy of creatine supplementation to alter mitochondrial markers as well as adipocyte size and multilocularity in inguinal (iWAT), gonadal (gWAT), and BAT. Thirty-two male and female Sprague-Dawley rats were treated with varying doses (0 g/L, 2.5 g/L, 5 g/L, and 10 g/L) of creatine monohydrate for 8 weeks. We demonstrate that mitochondrial markers respond in a sex and depot specific manner. In iWAT, female rats displayed significant increases in COXIV, PDH-E1alpha, and cytochrome C protein content. Male rats exhibited gWAT specific increases in COXIV and PDH-E1alpha protein content. This study supports creatine supplementation as a potential method of UCP1-independant thermogenesis and highlights the importance of taking a sex-specific approach when examining the efficacy of browning therapeutics in future research.

Sex- and tissue-dependent creatine uptake in response to different creatine monohydrate doses in male and female Sprague-Dawley rats.

Sprague-Dawley rats (n = 32) underwent 8-weeks of creatine monohydrate (CM) supplementation (0, 2.5, 5, and 10 g/L). Total creatine (TCr) concentrations in female white fibre-dominant gastrocnemius (WGAS) and cardiac muscle (HRT) were significantly higher compared with males (p < 0.05). CM supplementation increased TCr concentrations in female WGAS (p < 0.05) and HRT (p < 0.01) and in male red fibre-dominant gastrocnemius muscle (RGAS) (p < 0.05). Future research should further investigate sex-differences in basal levels of TCr and the response to CM supplementation. Novelty: There is a sex- and tissue-dependant response to CM supplementation in rats.