Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse

Area of Science:

• Physiology
• Obesity Research
• Thermoregulation

Background:

• Genetically obese (ob/ob) mice have impaired thermoregulation, particularly in response to cold.
• Previous research focused on intracellular metabolism or peripheral tissue insensitivity to catecholamines.

Purpose of the Study:

• To investigate sympathetic nervous system (SNS) activity in ob/ob mice as a potential factor in their defective thermoregulation.
• To measure norepinephrine (NE) turnover in key tissues to assess SNS function.

Main Methods:

• Norepinephrine (NE) turnover was measured in the heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice.
• Methods included using radiolabeled NE and inhibiting NE biosynthesis with alpha-methyl-p-tyrosine.
• SNS activity was assessed at ambient (22°C) and cold (4°C) temperatures.

Main Results:

• Ob/ob mice exhibited significantly reduced SNS activity (33-56% in heart, 45-73% in IBAT) compared to lean controls at 22°C.
• During cold exposure, NE turnover increased in both groups, but remained lower in ob/ob mice, correlating with hypothermia.
• Naltrexone administration did not reverse the suppressed SNS activity in ob/ob mice.

Conclusions:

• Diminished sympathetic nervous system (SNS) activity is a key factor contributing to the defective thermogenesis in genetically obese (ob/ob) mice.
• These findings suggest a central role for reduced SNS output in the pathophysiology of obesity-related thermoregulatory dysfunction.