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Anti-Obesity and Metabolic Effects of Forskolin in Obese C57BL/6J Mice

Mehrnaz Abbasi1,2, Fang Zhou1, Ngoc Kim Ly1

  • 1College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA.

International Journal of Molecular Sciences
|July 29, 2025
PubMed

Insights

Directly delivering forskolin (FSK) to white adipose tissue (WAT) in obese mice improved metabolic health and reduced obesity markers. This localized approach enhances anti-obesity effects and minimizes side effects compared to systemic administration.

Area of Science:

  • Metabolic disease research
  • Adipose tissue biology
  • Pharmacology

Background:

  • Forskolin (FSK) activates adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) to induce white adipose tissue (WAT) browning.
  • Systemic FSK administration leads to significant metabolism and off-target accumulation, causing side effects and limiting anti-obesity efficacy.
  • Local delivery strategies are needed to enhance therapeutic effects and reduce systemic toxicity.

Purpose of the Study:

  • To investigate the anti-obesity and metabolic effects of localized inguinal WAT (IWAT) delivery of FSK in diet-induced obese mice.
  • To compare the efficacy of different FSK dosages and delivery methods (bilateral vs. unilateral) into IWAT.
  • To assess the impact of local FSK delivery on adipocyte size, gene expression, and hepatic metabolism.

Main Methods:

  • Obese C57BL/6J mice received twice-weekly intra-IWAT injections of FSK (15 mg/kg or 7.5 mg/kg) or control for 4 weeks.
  • Evaluated metabolic parameters including blood glucose, glucose tolerance, serum insulin, and cholesterol levels.
  • Analyzed IWAT adipocyte morphology and quantified mRNA expression of key browning and inflammatory markers (Ucp1, Tmem26).
  • Assessed hepatic inflammatory and lipogenic markers to evaluate liver metabolism.

Main Results:

  • Both FSK dosages delivered bilaterally to IWAT improved glucose tolerance, lowered blood glucose, and reduced serum insulin and cholesterol.
  • The higher FSK dose (15 mg/kg) bilaterally enhanced IWAT browning, indicated by smaller adipocytes and increased Ucp1 and Tmem26 mRNA levels.
  • All FSK treatments reduced hepatic inflammatory and lipogenic markers, suggesting improved liver function.

Conclusions:

  • Local delivery of FSK into subcutaneous WAT represents a promising strategy for obesity management and metabolic health improvement.
  • Targeted delivery enhances FSK's anti-obesity effects and improves metabolic parameters more effectively than systemic administration.
  • Further research is warranted to confirm the clinical significance and optimize this localized therapeutic approach.
Keywords:
forskolinmetabolic healthobesitysubcutaneous WAT deliverywhite adipose tissue browning

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