Leptin signaling in adipose tissue: Role in lipid accumulation and weight gain

Prachi Singh, Timothy E. Peterson, Fatima H. Sert-Kuniyoshi, Jason A. Glenn, Diane E. Davison, Abel Romero-Corral, Snigdha Pusalavidyasagar, Michael Dennis Jensen, Virend Somers

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Rationale: The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1-dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. Objective: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. Methods and Results: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P=0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. Conclusions: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Original languageEnglish (US)
Pages (from-to)599-603
Number of pages5
JournalCirculation Research
Volume111
Issue number5
DOIs
StatePublished - Aug 17 2012

Fingerprint

Leptin
Weight Gain
Adipose Tissue
Caveolin 1
Lipids
Fatty Acid Synthases
Adipocytes
Longitudinal Studies
Volunteers
Cardiovascular Diseases
Obesity

Keywords

  • caveolin-1
  • impaired signaling
  • leptin
  • lipid accumulation
  • weight gain

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Singh, P., Peterson, T. E., Sert-Kuniyoshi, F. H., Glenn, J. A., Davison, D. E., Romero-Corral, A., ... Somers, V. (2012). Leptin signaling in adipose tissue: Role in lipid accumulation and weight gain. Circulation Research, 111(5), 599-603. https://doi.org/10.1161/CIRCRESAHA.112.273656

Leptin signaling in adipose tissue : Role in lipid accumulation and weight gain. / Singh, Prachi; Peterson, Timothy E.; Sert-Kuniyoshi, Fatima H.; Glenn, Jason A.; Davison, Diane E.; Romero-Corral, Abel; Pusalavidyasagar, Snigdha; Jensen, Michael Dennis; Somers, Virend.

In: Circulation Research, Vol. 111, No. 5, 17.08.2012, p. 599-603.

Research output: Contribution to journalArticle

Singh, P, Peterson, TE, Sert-Kuniyoshi, FH, Glenn, JA, Davison, DE, Romero-Corral, A, Pusalavidyasagar, S, Jensen, MD & Somers, V 2012, 'Leptin signaling in adipose tissue: Role in lipid accumulation and weight gain', Circulation Research, vol. 111, no. 5, pp. 599-603. https://doi.org/10.1161/CIRCRESAHA.112.273656
Singh P, Peterson TE, Sert-Kuniyoshi FH, Glenn JA, Davison DE, Romero-Corral A et al. Leptin signaling in adipose tissue: Role in lipid accumulation and weight gain. Circulation Research. 2012 Aug 17;111(5):599-603. https://doi.org/10.1161/CIRCRESAHA.112.273656
Singh, Prachi ; Peterson, Timothy E. ; Sert-Kuniyoshi, Fatima H. ; Glenn, Jason A. ; Davison, Diane E. ; Romero-Corral, Abel ; Pusalavidyasagar, Snigdha ; Jensen, Michael Dennis ; Somers, Virend. / Leptin signaling in adipose tissue : Role in lipid accumulation and weight gain. In: Circulation Research. 2012 ; Vol. 111, No. 5. pp. 599-603.
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