Leptin secretion and negative autocrine crosstalk with insulin in brown adipocytes

in Journal of Endocrinology
Authors:
D Kraus
Search for other papers by D Kraus in
Current site
Google Scholar
PubMed
Close
,
M Fasshauer
Search for other papers by M Fasshauer in
Current site
Google Scholar
PubMed
Close
,
V Ott
Search for other papers by V Ott in
Current site
Google Scholar
PubMed
Close
,
B Meier
Search for other papers by B Meier in
Current site
Google Scholar
PubMed
Close
,
M Jost
Search for other papers by M Jost in
Current site
Google Scholar
PubMed
Close
,
HH Klein
Search for other papers by HH Klein in
Current site
Google Scholar
PubMed
Close
, and
J Klein
Search for other papers by J Klein in
Current site
Google Scholar
PubMed
Close
Free access

Sign up for journal news

Leptin is an important adipocytokine whose main regulative effects on energy metabolism are exerted via activation of signalling pathways in the central nervous system. Another important regulator of energy homeostasis is insulin. The role of direct autocrine leptin effects on adipose tissue and crosstalk with insulin, in particular in the thermogenically active brown adipose tissue, remains unclear. In the present study, we have investigated leptin secretion and interaction with insulin in highly insulin-responsive immortalised mouse brown adipocytes. Leptin was secreted in a differentiation-dependent manner, and acute leptin treatment of mature adipocytes dose- and time-dependently stimulated phosphorylation of STAT3 and MAP kinase. Interestingly, acute pretreatment of fully differentiated brown adipocytes with leptin (100 nM) significantly diminished insulin-induced glucose uptake by approximately 25%. This inhibitory effect was time-dependent and maximal after 60 min of leptin prestimulation. Furthermore, it correlated with a 35% reduction in insulin-stimulated insulin receptor kinase activity after acute leptin pretreatment. Insulin-induced insulin receptor substrate-1 tyrosine phosphorylation and binding to the regulatory subunit p85 of phosphatidylinositol 3-kinase (PI 3-kinase) were diminished by approximately 60% and 40%, respectively. Taken together, this study has demonstrated strong differentiation-dependent leptin secretion in brown adipocytes and PI 3-kinase-mediated negative autocrine effects of this hormone on insulin action. Direct peripheral leptin-insulin crosstalk may play an important role in the regulation of energy homeostasis.

 

  • Collapse
  • Expand