👤 Sydney Pence

Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our previous studies have demonstrated reduced diet-induced thermogenesis in ApoA-IV-deficient mice, it is unclear whether this reduction is due to a loss of peripheral or central effects of ApoA-IV. We hypothesized that central administration of ApoA-IV stimulates BAT thermogenesis and that sympathetic and sensory innervation is necessary for this action. To test this hypothesis, mice with unilateral denervation of interscapular BAT received central injections of recombinant ApoA-IV protein or artificial cerebrospinal fluid (CSF). The effects of central ApoA-IV on BAT temperature and thermogenesis in mice with unilateral denervation of the intrascapular BAT were monitored using transponder probe implantation, qPCR, and immunoblots. Relative to CSF, central administration of ApoA-IV significantly increased temperature and UCP expression in BAT. However, all of these effects were significantly attenuated or prevented in mice with unilateral denervation. Together, these results clearly demonstrate that ApoA-IV regulates BAT thermogenesis centrally, and this effect is mediated through sympathetic and sensory nerves. Show less

In the presence of dietary lipids, both apolipoprotein A-IV (ApoA-IV) production and brown adipose tissue (BAT) thermogenesis are increased. The effect of dietary lipid-induced AproA-IV on BAT thermogenesis and energy expenditure remains unknown. In the present study, we hypothesized that ApoA-IV knockout (ApoA-IV-KO) mice exhibited decreased BAT thermogenesis to affect energy homeostasis. To test this hypothesis, BAT thermogenesis in wildtype (WT) and ApoA-IV-KO mice fed either a standard low-fat chow diet or a high-fat diet (HFD) was investigated. When fed a chow diet, energy expenditure and food intake were comparable between WT and ApoA-IV-KO mice. After 1 week of HFD consumption, ApoA-IV-KO mice had comparable energy intake but produced lower energy expenditure relative to their WT controls in the dark phase. After an acute feeding of dietary lipids or 1-week HFD feeding, ApoA-IV-KO mice produced lower levels of uncoupling protein 1 (UCP1) and exhibited reduced expression of thermogenic genes in the BAT compared with WT controls. In response to cold exposure, however, ApoA-IV-KO mice had comparable energy expenditure and BAT temperature relative to WT mice. Thus, ApoA-IV-KO mice exhibited reduced diet-induced BAT thermogenesis and energy expenditure. Show less