Induction of mitochondrial uncoupling enhances VEGF₁₂₀ but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways

Biochemical and Biophysical Research Communications
Kaoru Miyokawa-GorinHitoshi Ishida

Abstract

Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (p<0.01) in 24h DNP (30 μmol/L)-treated adipocytes compared to control cells. In contrast, secreted VEGF(120) lacking a heparin-binding domain was markedly increased 2.0-fold (p<0.01). CHOP content in these cells also were augmented (p<0.01), but no significant increase of endogenous oxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (p<0.01), but exhibited no effects on VEGF(120) secretion. On the other hand, exogenous H(2)O(2) amplified both MCP-1 and VEGF(120) secretion (p<0.05). In addition, under chronic activation of AMPK by AICAR, MCP-1 release was significantly diminished (p<0.05) but VEGF(120) secretion was increased (p<0.01). JNK...Continue Reading

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Citations

Feb 11, 2014·Journal of Translational Medicine·Li DongChengshui Chen
Jan 8, 2013·Biochemical and Biophysical Research Communications·Nobuhiko TakahashiMasahiro Ieko
Aug 12, 2014·Biochemical and Biophysical Research Communications·Hirohisa OnumaHitoshi Ishida
Oct 16, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J JovenJ A Menéndez
Jul 10, 2013·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Bareket DanielArie Gruzman
Jan 15, 2015·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Y Bai, Q Sun
Jun 6, 2021·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Qiao YuRong Lin

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