Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats

Aroa Jimenéz-Aranda, Gumersindo Fernández-Vázquez, María Mohammad A-Serrano, Russel J Reiter, Ahmad Agil

Research output: Contribution to journalArticle

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Abstract

Mitochondrial dysfunction in adipose tissue may contribute to obesity-related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity-related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats mainly through a reduction of proton leaking component of respiration (state 4) (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05) and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled respiration. Melatonin also lowered mitochondrial oxidative status by reducing nitrite levels and by increasing superoxide dismutase activity. Moreover, melatonin treatment also caused a profound inhibition of Ca-induced opening of mPTP in isolated mitochondria from both types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity-related metabolic disorders such as diabetes and dyslipidemia of ZDF rats.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalJournal of Pineal Research
Volume57
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

White Adipose Tissue
Groin
Melatonin
Mitochondria
Obesity
Type 2 Diabetes Mellitus
Respiration
White Adipocytes
Metabolome
Respiratory Rate
Dyslipidemias
Nitrites
Drinking Water
Organelles
Superoxide Dismutase
Protons
Adipose Tissue
Theoretical Models
Apoptosis

Keywords

  • beige adipose tissue
  • melatonin
  • mitochondrial function
  • white adipose tissue
  • Zücker diabetic fatty rats

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)

Cite this

Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats. / Jimenéz-Aranda, Aroa; Fernández-Vázquez, Gumersindo; Mohammad A-Serrano, María; Reiter, Russel J; Agil, Ahmad.

In: Journal of Pineal Research, Vol. 57, No. 1, 2014, p. 103-109.

Research output: Contribution to journalArticle

Jimenéz-Aranda, Aroa ; Fernández-Vázquez, Gumersindo ; Mohammad A-Serrano, María ; Reiter, Russel J ; Agil, Ahmad. / Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats. In: Journal of Pineal Research. 2014 ; Vol. 57, No. 1. pp. 103-109.
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