Researcher's Profile

Obesity is a major cause of cardiovascular diseases, cerebrovascular diseases, hepatic steatosis and certain types of cancer. Although reducing dietary intake and increasing physical activity constitute logical ways to tip energy balance toward weight loss, sustained interventions are rather difficult to achieve owing to poor adherence of lifestyle changes. Indeed, prevalence of obesity has been increasing worldwide: there is an urgent need for effective treatments. In this regard, thermogenic adipocytes (i.e., brown and beige adipocytes) are promising targets because these cells contribute to adaptive thermogenesis and energy expenditure in response to environmental cues, including temperatures (e.g., cold exposure). The identification of novel molecular circuits that control adipocyte thermogenesis may lead to the discovery of targetable pathways for the development of pharmacotherapies for metabolic diseases.

We previously demonstrated that energy-consuming ability of thermogenic adipocytes are controlled through epigenetic mechanisms induced by cold exposure. Our current study examines a hypothesis that cold-induced epigenomes in father mice may be inherited by offspring mice to preprogram thermogenic activity of brown/beige adipocytes. To unveil molecular mechanisms of this transgenerational inheritance, we apply the cutting-edge technologies (e.g., comprehensive analysis of epigenomes, single-cell RNA sequence) as well as the classical biological/biochemical approaches (e.g., mouse genetics, molecular biology). We also examine its clinical relevance by investigating impacts of seasonal cold exposure prior to fertilization on brown/beige adipocyte activity in healthy human volunteers. Furthermore, we investigate cellular heterogeneity of brown/beige adipocytes as well as mechanisms of the cell fate determination which may be potentially variable for developing new strategies to activate highly thermogenic cell types.

Our long-term goal is to use our scientific insights to establish effective interventions to treat obesity and metabolic diseases.