Abstract
Oxidation of fat by brown adipose tissue (BAT) contributes to energy balance and heat production. During cold exposure, BAT thermogenesis produces heat to warm the body. Obese subjects and rodents, however, show impaired BAT thermogenesis to the cold. Our previous studies suggest that vagal afferents synapsing in the nucleus tractus solitarius (NTS), tonically inhibit BAT thermogenesis to the cold in obese rats. NTS neurons send projections to the dorsal aspect of the lateral parabrachial nucleus (LPBd), which is a major integrative center that receives warm afferent inputs from the periphery and promotes inhibition of BAT thermogenesis. This study investigated the contribution of LPBd neurons in the impairment of BAT thermogenesis in rats fed a high-fat diet (HFD). By using a targeted dual viral vector approach, we found that chemogenetic activation of an NTS-LPB pathway inhibited BAT thermogenesis to the cold. We also found that the number of Fos-labelled neurons in the LPBd was higher in rats fed a HFD than in chow diet-fed rats after exposure to a cold ambient temperature. Nanoinjections of a GABAA receptor agonist into the LPBd area rescued BAT thermogenesis to the cold in HFD rats. These data reveal the LPBd as a critical brain area that tonically suppresses energy expenditure in obesity during skin cooling. These findings reveal novel effects of high-fat diets in the brain and in the control of metabolism and can contribute to the development of therapeutic approaches to regulate fat metabolism.