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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Polymethoxyflavones activate Ca2+-dependent apoptotic targets in adipocytes.
Igor N Sergeev1, Shiming Li, Chi-Tang Ho
1Department of Nutrition, Food Science, South Dakota State University, Brookings, South Dakota 57007, USA. igor.sergeev@sdstate.edu
Journal of Agricultural and Food Chemistry
|June 16, 2009
Summary
Polymethoxyflavones (PMFs) trigger apoptosis in fat cells by increasing intracellular calcium, activating calpain and caspase-12. This discovery offers a new strategy for obesity treatment and long-lasting weight management.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Disorders
Background:
- Apoptosis (programmed cell death) of adipocytes is a promising strategy for obesity treatment.
- Polymethoxyflavones (PMFs) have shown apoptosis-inducing effects in cancer cells via calcium signaling.
- Intracellular calcium (Ca2+) plays a key role in apoptosis induction.
Purpose of the Study:
- To investigate the effect of PMFs on apoptosis in mature mouse 3T3-L1 adipocytes.
- To elucidate the molecular mechanisms underlying PMF-induced adipocyte apoptosis, focusing on calcium signaling pathways.
Main Methods:
- Treatment of 3T3-L1 adipocytes with varying concentrations and durations of PMFs.
- Measurement of intracellular Ca2+ levels.
- Assay of calpain and caspase-12 activity.
- Assessment of apoptosis induction.
Main Results:
- PMFs induced apoptosis in 3T3-L1 adipocytes in a concentration- and time-dependent manner.
- PMF treatment led to a sustained increase in intracellular Ca2+ levels.
- This increase in Ca2+ was associated with the activation of mu-calpain and caspase-12.
- Hydroxylated PMFs exhibited significantly higher apoptosis-inducing activity compared to nonhydroxylated forms.
Conclusions:
- PMFs induce adipocyte apoptosis through the activation of Ca2+-dependent calpain and caspase-12.
- These findings support the potential of PMFs as therapeutic agents for obesity prevention and treatment by targeting fat cell reduction.
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