Chronic High-Fat Diet Exacerbates Sexually Dimorphic Pomctm1/tm1 Mouse Obesity

Area of Science:

• Endocrinology
• Obesity Research
• Neuroscience

Background:

• Pro-opiomelanocortin (Pomc) deficiency leads to obesity in mice.
• The role of Pomc in diet-induced obesity, particularly sex differences, requires further investigation.

Purpose of the Study:

• To investigate if a chronic high-fat (HF) diet exacerbates obesity in Pomc-deficient mice (Pomctm1/tm1).
• To determine the sex-specific mechanisms underlying diet-induced obesity in Pomc-deficient mice.

Main Methods:

• Male and female Pomc-deficient (Pomctm1/tm1) and wild-type (Pomcwt/wt) mice were fed low-fat (LF) or HF diets for 23 weeks.
• Body weight, feed efficiency, energy intake, and energy expenditure were monitored.

Main Results:

• Pomctm1/tm1 mouse obesity is sexually dimorphic and worsened by HF diet.
• Male Pomctm1/tm1 mice are hyperphagic on both LF and HF diets.
• Female Pomctm1/tm1 mice exhibit reduced energy expenditure on both diets, exacerbated by HF diet.
• Wild-type females are protected from HF diet obesity by reducing intake and increasing energy expenditure.
• Pomc deficiency impairs these protective mechanisms in females.

Conclusions:

• Desacetyl-α-MSH and α-MSH are crucial for regulating sexually dimorphic responses to HF diet-induced obesity.
• Pomc signaling is essential for preventing obesity in response to dietary challenges in a sex-dependent manner.