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Wnt10b inhibits obesity in ob/ob and agouti mice
Wendy S Wright1, Kenneth A Longo, Vernon W Dolinsky
1Department of Molecular and Integrative Physiology, University of Michigan, 1301 E. Catherine Drive, Ann Arbor, MI 48109-0622, USA.
Abstract:
The Wnt family of secreted signaling molecules has profound effects on diverse developmental processes, including the fate of mesenchymal progenitors. While activation of Wnt signaling blocks adipogenesis, inhibition of endogenous Wnt/beta-catenin signaling by Wnt10b promotes spontaneous preadipocyte differentiation. Transgenic mice with expression of Wnt10b from the FABP4 promoter (FABP4-Wnt10b) have less adipose tissue when maintained on a normal chow diet and are resistant to diet-induced obesity. Here we demonstrate that FABP4-Wnt10b mice largely avert weight gain and metabolic abnormalities associated with genetic obesity. FABP4-Wnt10b mice do not gain significant body weight on the ob/ob background, and at 8 weeks of age, they have an approximately 70% reduction in visceral and subcutaneous adipose tissues compared with ob/ob mice. Similarly, on the lethal yellow agouti (A(y)) background, FABP4-Wnt10b mice have 50-70% less adipose tissue weight and circulating leptin at 5 months of age. Wnt10b-Ay mice are more glucose tolerant and insulin sensitive than A(y) controls, perhaps due to reduced expression and circulation of resistin. Reduced expression of inflammatory cytokines may also contribute to improved glucose homeostasis.
Insights
Wnt10b expression in mice prevents obesity and related metabolic issues. These mice show reduced adipose tissue and improved glucose metabolism, highlighting Wnt signaling
Area of Science:
- Molecular Biology
- Developmental Biology
- Metabolic Research
Background:
- The Wnt signaling pathway regulates mesenchymal progenitor cell fate and adipogenesis.
- Wnt10b specifically inhibits adipogenesis, while its absence promotes preadipocyte differentiation.
- FABP4-Wnt10b transgenic mice exhibit reduced adipose tissue and resistance to diet-induced obesity.
Purpose of the Study:
- To investigate the effects of FABP4-Wnt10b expression on genetic obesity models.
- To assess the impact of Wnt10b on body weight, adipose tissue mass, and metabolic parameters in obese mice.
Main Methods:
- Generation of FABP4-Wnt10b transgenic mice.
- Crossing FABP4-Wnt10b mice with ob/ob and lethal yellow agouti (A(y)) genetic obesity models.
- Analysis of body weight, adipose tissue depots (visceral and subcutaneous), circulating leptin, glucose tolerance, and insulin sensitivity.
Main Results:
- FABP4-Wnt10b mice on the ob/ob background showed no significant weight gain and a ~70% reduction in adipose tissue.
- FABP4-Wnt10b mice on the A(y) background exhibited 50-70% less adipose tissue and lower leptin levels.
- Wnt10b-A(y) mice demonstrated improved glucose tolerance and insulin sensitivity, potentially linked to reduced resistin and inflammatory cytokines.
Conclusions:
- FABP4-driven Wnt10b expression effectively prevents weight gain and ameliorates metabolic abnormalities in genetic models of obesity.
- Wnt10b plays a crucial role in regulating adipose tissue mass and improving metabolic homeostasis.
- Targeting Wnt10b signaling represents a potential therapeutic strategy for obesity and associated metabolic disorders.
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