Aging-Induced Brain-Derived Neurotrophic Factor in Adipocyte Progenitors Contributes to Adipose Tissue Dysfunction

Area of Science:

• Metabolic disease
• Adipose tissue biology
• Aging research

Background:

• Aging adipose tissue dysfunction contributes to chronic metabolic diseases.
• Brain-derived neurotrophic factor (BDNF) plays a role in adipose tissue.
• Age-dependent changes in adipose tissue impact metabolic health.

Purpose of the Study:

• Investigate the role of age-dependent brain-derived neurotrophic factor (BDNF) expression in adipose tissue.
• Determine the effect of BDNF in adipocyte progenitors on adipose tissue aging.
• Explore potential therapeutic targets for aging-related metabolic dysfunction.

Main Methods:

• Assessed pro-BDNF expression in aged epididymal white adipose tissue (eWAT).
• Isolated and analyzed BDNF expression in PDGFRα+ adipocyte progenitors.
• Utilized tamoxifen-inducible PDGFRα+ cell-specific deletion of BDNF (BDNFPdgfra KO) in mice.
• Evaluated sympathetic innervation, mitochondrial content, insulin sensitivity, and inflammation markers in eWAT.

Main Results:

• Pro-BDNF expression increased in aged eWAT, correlating with reduced sympathetic innervation.
• BDNF expression was enriched in PDGFRα+ adipocyte progenitors, with age-dependent upregulation.
• BDNFPdgfra KO mice showed preserved sympathetic innervation and mitochondrial content, improved insulin sensitivity, and reduced inflammation and senescence markers.
• In vitro pro-BDNF treatment induced adipocyte apoptosis, mitigated by sortilin knockdown.

Conclusions:

• Upregulation of pro-BDNF in adipocyte progenitors is a key feature of visceral white adipose tissue aging.
• Targeting BDNF in adipocyte progenitors may offer a strategy to combat aging-related adipose tissue dysfunction.
• This research highlights BDNF as a potential therapeutic target for age-associated metabolic diseases.