Leptin and adiponectin synthesis and secretion in mature 3T3-L1 adipocytes are differentially down-regulated by arsenic and palmitic acid exposure throughout different stages of adipogenesis

Life Sci. 2022 Feb 15:291:120262. doi: 10.1016/j.lfs.2021.120262. Epub 2021 Dec 28.

Abstract

Aims: Arsenic is a risk factor for type 2 diabetes and cardiovascular disease. However, little is known about arsenic effects over adipocyte endocrine functionality, particularly for leptin and adiponectin, and about its interaction with dietary components, which are the main environmental regulators of adipose tissue functionality. The aim of this work was to evaluate leptin and adiponectin in mature 3T3-L1 adipocytes exposed to palmitate (simulating excess fat intake), arsenite, or both throughout two different stages of adipogenesis.

Material and methods: 3T3-L1 adipocytes were exposed starting from the beginning of its differentiation process during 11 d or once adipocytes were mature for 72 h. Adipokines secretion was evaluated by ELISA, intracellular protein levels and secreted adiponectin multimers by Western blot and mRNA abundance by qPCR.

Key findings: Leptin and adiponectin secretion decreased by arsenite alone or in combination with palmitate due to reduced gene and protein expression of both adipokines. However, leptin was impaired more at the transcriptional level, whereas affections to adiponectin were more relevant at the intracellular protein amount level with changes in the multimers proportion. The gene expression of several of their transcription factors was altered. Additionally, the magnitude of the effects depends on the adipocyte cell stage at which exposure began; adiponectin was more affected when exposure started from differentiation and leptin once adipocytes were mature.

Significance: These results in an in vivo model could be translated into less satiety and reduced insulin sensitivity.

Keywords: Adipocyte; Adiponectin; Arsenic; Leptin; Palmitic acid.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / physiology*
  • Adipokines / metabolism
  • Adiponectin / metabolism*
  • Animals
  • Arsenic / metabolism
  • Arsenites / pharmacology
  • Arsenites / toxicity
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Insulin / metabolism
  • Insulin Resistance
  • Leptin / metabolism*
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Mice
  • Palmitic Acid / pharmacology

Substances

  • Adipokines
  • Adiponectin
  • Arsenites
  • Insulin
  • Leptin
  • Palmitic Acid
  • arsenite
  • Arsenic