MnTBAP reduces diet‐induced adiposity independent of β‐adrenergic receptor signaling (854.8)

Abstract

Manganese tetrakis benzoic acid porphyrin (MnTBAP) is a superoxide dismutase mimetic that has recently been shown to reduce visceral adiposity (Pires et al., 2013). In visceral fat of mice treated with MnTBAP, we have observed significant increases in hormone sensitive lipase activity and PGC‐1α expression. These observations indicate that MnTBAP may activate the sympathetic nervous system, which is known to stimulate lipolysis and brown/beige adipocyte activity. To test whether the ability of MnTBAP to reduce adiposity is dependent on β‐adrenergic receptor signaling, mice were fed a high fat diet (HFD) or a low fat diet (LFD) for six months. During the last six weeks of the dietary intervention mice were treated with MnTBAP alone or in combination with a β‐adrenergic receptor antagonist cocktail (β‐Blockers) containing propranolol and the β3‐adrenergic receptor antagonist SR59230A. Prior to treatment, mice fed a HFD weighed significantly more than mice fed a LFD, but no significant differences in body weight were observed among mice receiving vehicle, MnTBAP, or MnTBAP+β‐Blockers within a respective diet condition. Following the six week treatment period, mice fed a HFD that received MnTBAP or MnTBAP+β‐Blockers experienced a significant reduction in body weight and epididymal white adipose tissue (EWAT) mass than mice that received vehicle. These changes appeared to be related to caloric intake but not energy expenditure, as mice that received MnTBAP or MNTBAP+β‐Blockers consumed significantly less calories and had decreased energy expenditure compared to vehicle‐treated controls. Finally, there was no effect of MnTBAP treatment on UCP1 or Cidea expression in EWAT. Collectively, these results suggest that the ability of MnTBAP to reduce adiposity is independent of β‐adrenergic receptor signaling and indicate that MnTBAP decreases adiposity by regulating caloric intake.Grant Funding Source: Supported by NIH 1 R15 DK090722‐01