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Topical Area: Obesity

Obesity (Poster Session)

(P31-001-23) Anti-Obesity and Metabolic Effects of Forskolin in Obese C57BL/6J Mice

Monday, July 24, 2023
11:45 AM – 12:45 PM ET
Location: Poster Board 224

    Presenting Author(s)

  • Mehrnaz Abbasi, PhD

    Postdoctoral Scholar
    Arizona State University
    Phoenix, Arizona, United States

    • Co-Author(s)

  • Fang Zhou

    PhD student, RA
    Arizona State University
    Tempe, Arizona, United States

  • QH

    Qiaobin Hu, PhD

    Postdoctoral Research Scientist
    Arizona State University
    Phoenix, Arizona, United States

  • SW

    Shu Wang, MD, PhD

    Faculty
    Arizona State University
    Phoenix, Arizona, United States

Disclosure(s):
Mehrnaz Abbasi, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Fang Zhou: No relevant financial relationship(s) with ineligible companies to disclose.
Qiaobin Hu, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Browning white adipose tissue (WAT) is a promising approach to combating obesity and its comorbidities. Forskolin (FSK), found in the Coleus forskohlii plant roots, can induce WAT browning via increasing adenylate cyclase activity. However, its low WAT target specificity and high toxicity at high doses make it unrealistic in treating obesity. The objectives of this study are to investigate the browning effect of FSK via WAT injection in obese mice, and to investigate the underlying mechanisms.

Methods: Six-week-old male C57BL/6 mice were fed a high-fat diet for 9 weeks. After 4 weeks, mice were randomly assigned to one of 4 groups: 1. FSK dissolved in Tween80 (FSK-T), 2. FSK dissolved in Cremophor EL (FSK-C), 3. Control Tween80 (Con-T), 4. Control Cremophor EL (Con-C). Doses of FSK-T and FSK-C were 15 and 20 mg/kg body weight, respectively. Treatments were directly injected into inguinal WAT (IgWAT) twice per week for 5 weeks. Food intake, body weight, and body composition were measured weekly. A glucose tolerance test (GTT) was conducted at week 8, and energy expenditure, and cold tolerance test were conducted at week 9. Blood triglyceride levels, and liver and kidney function panels were measured.

Results: Mice treated with FSK-C or FSK-T compared to controls had significantly lower body weight, body fat%, the area under the curve of GTT, and increased energy expenditure. FSK-C or FSK-T treatments decreased mRNA expression of inflammatory markers MCP1, TNF , and IL6, and lipogenic markers SCD1, FAS, ACC1, and CPT in IgWAT. FSK-C- treated mice had increased mRNA levels of browning markers PRDM16, ELOVL3, and PRDM16 in IgWAT, and maintained their core temperature at 37°C during the cold tolerance test. FSK-C decreased blood triglyceride levels. Liver and kidney function measures were not significant different among four groups.

Conclusions: Local delivery of FSK into subcutaneous WAT decreased body weight and fat mass, improved glucose homeostasis, increased expression of browning marker genes, and decreased expression of inflammatory and lipogenic genes in subcutaneous WAT. It might be a promising approach for combating obesity and improving metabolic health.

Funding Sources: This work was supported by Grant Number 1R15AT010395 from the NIH, and Grant Number 19AIREA34480011 from American Heart Association.