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(AL05-01-26) Fluctuation of Energy and Hormones Attenuates PPARgamma and Remodels Lipid Droplet-Coating Proteins in a Yo-Yo Model of Human Adipocytes

Monday, July 27, 2026
3:30 PM - 3:45 PM ET
Location: Maryland Ballroom B
George Bray Obesity Research Student Awards

    Presenting Author(s)

  • JK

    Judy Kim, PhD

    Ph.D.
    University of Massachusetts, Amherst
    Sunderland, Massachusetts, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • YK

    Young-Cheul Kim

    University of Massachusetts Amherst, United States

  • SC

    Soonkyu Chung

    University of Massachusetts Amherst, United States

Disclosure(s):
Judy Kim, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Yo-yo dieting is the repeated fluctuations in energy intake accompanied by cyclical hormonal changes and is strongly associated with weight regain and metabolic dysfunction. However, the cellular mechanisms underlying these effects remain poorly understood. We developed an in vitro yo-yo model of human adipocytes to investigate how repeated energy and hormonal fluctuations/alterations affect adipocyte lipid metabolism and endocrine function.

Methods: Immortalized human white preadipocytes were differentiated into adipocytes, with ~50% of adipogenic conversion. Yo-yo adipocytes (Yoyo-Ad) underwent two cycles of 48 h low-energy conditions (low glucose, serum, and free fatty acids with norepinephrine) followed by 48 h energy-surplus conditions (high glucose, serum, FFA, and insulin). Control adipocytes (Con-Ad) were maintained in standard adipocyte maintenance medium. Lipid accumulation was assessed by Oil Red O staining. Adipocyte morphology was evaluated by lipid droplet–coating proteins. Lipolysis was measured by glycerol release, and endocrine factor expression was analyzed by qPCR and Western blot.

Results: Yoyo-Ad significantly increased lipid accumulation despite reduced express of PPARγ and its lipogenic target genes. This phenotype was linked with a marked increase in PREF1 expression and small lipid droplets coated with Perilipin 2 in the non-adipocyte fraction, along with a loss of Perilipin 1–coated lipid droplets in mature adipocytes. Consistently, Yoyo-Ad increased basal lipolysis but reduced stimulated lipolysis, indicating impaired adipocyte lipid storage capacity. In addition, Yoyo-Ad significantly decreased leptin and adiponectin expression while increasing DPP-4 expression and activity.

Conclusions: This in vitro study establishes yo-yo adipocyte model that recapitulates phenotypic, metabolic, and endocrine alterations linked to weight cycling. Our findings identify attenuation of PPARγ and remodeling of lipid droplet coating proteins as potential mechanisms linking repeated energy fluctuations to observed in vivo and identifies PPARγ attenuation as a key mechanism underlying yo-yo dieting–induced metabolic dysfunction.

Funding Sources: N/A