Cited by 38Adipokines, Inflammation, and Metabolic DiseasesLipid metabolism and biosynthesisAdipose Tissue and Metabolism

Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

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Lee, Mi-Jeong, Fried, Susan K.·2012·American Journal of Physiology-Endocrinology and Metabolism

Abstract

High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX), or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone did not significantly affect lipolysis. Cotreatment with DEX blocked TNF induction of basal lipolysis and insulin resistance by antagonizing TNF stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at Ser 563 and Ser 660 and perilipin. TNF did not affect perilipin, HSL, or phosphodiesterase-3B mass but paradoxically suppressed adipose tissue triglyceride lipase expression, and this effect was blocked by DEX. The extent to which GCs can restrain the lipolytic actions of TNF may both diminish the potentially deleterious effects of excess lipolysis and contribute to fat accumulation in obesity.

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Crossref · 10.1152/ajpendo.00228.2012

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Authors
Lee, M.-J., & Fried, S. K.
Affiliations
Boston University (US)
Corresponding author
Lee, Mi-Jeong
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2012-11-01
Volume
303
Issue
9
Pages
E1126-E1133
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2131270144
Cited by
38
References
46
Citations by year
2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 8 · 2013: 4
FWCI
3.59
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK52398, P30DK046200, R01DK052398, DK080448, R01DK080448)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
glucocorticoids, TNF-α, lipolysis, insulin resistance, adipocytes, dexamethasone, hormone-sensitive lipase, perilipin, PDE3B, obesity, insulin signaling, protein kinase A phosphorylation
MeSH terms
Perilipin-1, Acyltransferases, Adult, Carrier Proteins, Cells, Cultured, Sterol Esterase, Dexamethasone, Female, Gene Expression Regulation, Glucocorticoids, Humans, Insulin, Insulin Resistance, Lipase, Lipolysis, Male, Middle Aged, Phosphoproteins, Phosphorylation, Protein Processing, Post-Translational, Tumor Necrosis Factor-alpha, Cyclic AMP-Dependent Protein Kinases, Tissue Culture Techniques, Subcutaneous Fat, Abdominal, Cyclic Nucleotide Phosphodiesterases, Type 3

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