CTRP13 ablation improves systemic glucose and lipid metabolism.

Area of Science:

• Endocrinology
• Metabolic Regulation
• Molecular Biology

Background:

• Secreted hormones mediate tissue crosstalk for integrated metabolic control.
• CTRP13 (C1q family) improves glucose metabolism and insulin action in vitro, and reduces body weight and food intake in mice.
• Previous studies indicated CTRP13 regulates insulin secretion, but its physiological role in metabolic homeostasis remained unclear.

Purpose of the Study:

• To investigate the physiological function of CTRP13 in metabolic homeostasis using a loss-of-function mouse model.
• To determine if CTRP13 is essential for maintaining metabolic balance.
• To explore the impact of CTRP13 deficiency on glucose and lipid metabolism, and systemic metabolic profiles.

Main Methods:

• Generated and studied Ctrp13 knockout (KO) mice under standard chow and high-fat diet conditions.
• Performed comprehensive metabolic phenotyping, including glucose tolerance and insulin sensitivity tests.
• Conducted transcriptomic analyses on key metabolic tissues (fat, liver, muscle) and integrated data with human cohort data (METSIM).

Main Results:

• Ctrp13-KO mice exhibited increased physical activity, reduced body weight, and improved lipid handling, independent of diet.
• Loss of CTRP13 enhanced glucose tolerance, insulin sensitivity, and triglyceride clearance, with notable sex differences.
• Transcriptomic data revealed reduced inflammation and hepatic steatosis in KO mice, with suppressed lipid synthesis and enhanced catabolism.

Conclusions:

• CTRP13 acts as a negative regulator of metabolism; its deficiency improves systemic metabolic profiles.
• Reduced circulating CTRP13 levels in human obesity and diabetes may represent a compensatory mechanism against insulin resistance.
• CTRP13 deficiency significantly impacts gene expression in adipose tissue, suggesting a causal role in human metabolic syndrome.