Biology subjects

Chow, L. S.

Publications and source records attributed to Chow, L. S..

2 recordsLinked to original sources

bioRxiv2025

Ketone body driven lipid remodeling supports thermogenic adaptation to fasting

Metabolic adaptation to fasting may have conferred survival advantage to early humans and predicts weight gain caused by overnutrition in modern societies. Fasting suppresses brown adipose tissue (BAT) thermogenesis; however, it is unclear how BAT rewires cellular metabolism to balance between energy conservation and heat generation. Here, we report that BAT in mice under fasting and cold challenge consumed ketone bodies, specifically acetoacetate (AcAc). Ablating liver ketogenesis decreased, while enhancing hepatic AcAc output defended, body temperature in mice facing the dual challenge. Using stable isotope tracing in brown adipocytes in vitro combined with quantitative analysis of metabolic fluxes and lipidomics in BAT from genetic mouse models, we disentangled the two metabolic fates of AcAc - terminal oxidation in the mitochondria and lipid biosynthesis in the cytosol. Notably, AcAc-sourced carbon preferentially supported polyunsaturated fatty acid synthesis in BAT, linking to the positive impact of intermittent fasting on lipid profiles in both mice and humans. Therefore, ketone body utilization by thermogenic adipocytes contributes to metabolic resilience of mammals and can be targeted to optimize benefits of dietary regimens.

physiology↗

bioRxiv2023

Gender-based heterogeneity of FAHFAs in trained runners

Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in trained runners. Here we compared the association between circulating FAHFA baseline concentrations and body composition, determined by dual x-ray absorptiometry, in female runners who were lean (BMI < 25 kg/m2, n = 6), to those who were overweight (BMI [≥] 25 kg/m2, n = 7). We also compared circulating FAHFAs in lean male runners (n = 8) to the same trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but, strikingly, in both lean and overweight cohorts, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.

physiology↗