1. Academic Validation
  2. Inhibitory effects of naringenin on estrogen deficiency-induced obesity via regulation of mitochondrial dynamics and AMPK activation associated with white adipose tissue browning

Inhibitory effects of naringenin on estrogen deficiency-induced obesity via regulation of mitochondrial dynamics and AMPK activation associated with white adipose tissue browning

  • Life Sci. 2024 Jan 23:340:122453. doi: 10.1016/j.lfs.2024.122453.
Tong Pan 1 Yen-Mei Lee 1 Eiki Takimoto 2 Kazutaka Ueda 3 Pang-Yen Liu 4 Hsin-Hsueh Shen 1
Affiliations

Affiliations

  • 1 Graduate Institute and Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
  • 2 Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
  • 3 Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
  • 4 Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: liupy@mail.ndmctsgh.edu.tw.
Abstract

Aims: Post-ovariectomy (OVX) changes in Hormones induce obesity and white adipose tissue (WAT) inflammation. Increased energy expenditure via WAT browning is a novel therapeutic strategy for treating obesity. Naringenin (NAR) reduces inflammation and lipogenesis in obesity and attenuates estrogen deficiency-associated metabolic disorders; however, its role in WAT browning remains unclear.

Materials and methods: We investigated NAR ability to inhibit estrogen deficiency-associated obesity in vivo using a rat model and in vitro using 3T3-L1 adipocytes.

Key findings: NAR significantly decreased the body weight and WAT mass of rats. O2 consumption, CO2 production, and energy expenditure were significantly lower in the OVX group than in the sham group, but NAR treatment reversed these effects of OVX. NAR treatment markedly improved glucose intolerance and lipid profiles as well as Leptin, Adiponectin, and irisin levels. NAR upregulated markers of browning and mitochondrial biogenesis in inguinal WAT. Moreover, it enhanced markers of mitochondrial fusion and inhibited fission via activating the AMP-activated protein kinase pathway. Similar results were observed in 3T3-L1 adipocytes. Moreover, NAR-induced mitochondrial biogenesis and fusion were suppressed by dorsomorphin (an AMP-activated protein kinase inhibitor).

Significance: NAR alleviates obesity and metabolic dysfunction through the induction of WAT browning achieved via the modulation of AMP-activated protein kinase-regulated mitochondrial dynamics in WATs. NAR supplementation may therefore represent a potential intervention for preventing postmenopausal adipose tissue dysregulation.

Keywords

Browning; Inflammation; Mitochondrial dynamics; Naringenin; Ovariectomy; White adipose tissue.

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