Obesity • diabetes • hypothalamus • leptin receptor • leptin sensing • NG2-glia • neuroendocrinology • genetic mouse models
Obesity is a major health threat reaching pandemic proportions and is a strong risk factor for many diseases, particularly type 2 diabetes. However, effective counter-measures are still largely lacking. Energy balance crucially depends on specialized brain circuits that process signals from peripheral organs and the environment to control food intake and energy expenditure. Central to the body’s ability to limit fat mass accumulation is the adipocyte-derived hormone leptin, which acts on the major energy balance control circuits located in the hypothalamus. Although it has long been known that several subtypes of neurons located primarily in the arcuate nucleus of the hypothalamus respond to leptin, precisely how and where circulating leptin is sensed is still unresolved. Our research aims to clarify mechanisms of leptin sensing in general and in the context of age-related weight gain. The long-term goal of my lab is to clarify why some humans can maintain their body weights strikingly constant over most of their adult lives while others are confronted with gradual or abrupt increases in fat mass as they age. Our studies may thus provide new insight into the etiology of obesity and ultimately help to develop new strategies for the prevention and treatment of obesity and obesity-related diseases.
Robins SC, Kokoeva MV. NG2-Glia, a New Player in Energy Balance. Neuroendocrinology. 2018;107(3):305-312. PMID: 29506015.
Djogo T, Robins SC, Schneider S, Kryzskaya D, Liu X, Mingay A, Gillon CJ, Kim JH, Storch KF, Boehm U, Bourque CW, Stroh T, Dimou L, Kokoeva MV. Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control. Cell Metabolism. 2016 May 10;23(5):797-810. PMID: 27166944.
Blum ID, Zhu L, Moquin L, Kokoeva MV, Gratton A, Giros B, Storch KF. A highly tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal. Elife. 2014 Dec 29;3. PMID: 25546305.
Robins SC, Trudel E, Rotondia O, Liu X, Djogo T, Kryzskaya D, Bourque CW, & Kokoeva MV. Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus. PLoS ONE, 8:e78236. (2013). PMID: 24205170.
Robins SC, Villemain A, Liu X, Djogo T, Kryzskaya D, Storch K-F, & Kokoeva MV “Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal” Glia, 10:1735-47. (2013). PMID: 23918524.