Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes
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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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In vitro studies in adipocytes have shown lipolytic rates to be increased, unchanged or decreased by glucocorticoids.
“For example, in vitro studies in adipocytes have shown lipolytic rates to be increased,4 unchanged5 or decreased6 by glucocorticoids.”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [5]
Insulin and adrenaline are critical confounders in the effects of glucocorticoids on lipolysis.
“Over and above prevailing glucocorticoid concentrations, a further critical confounder is the effect of other hormones regulating lipolysis, notably insulin and adrenaline.5, 6”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [5]
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Self-citation
- Authors
- Lee, M.-J., & Fried, S. K.
- Affiliations
- Boston University (US)
- Corresponding author
- Lee, Mi-Jeong
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2012-11-01
- Volume
- 303
- Issue
- 9
- Pages
- E1126-E1133
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3492859
- 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
- green
- europepmc.org
- 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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