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Updated: May 30, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
The Ca2+/calmodulin-dependent protein kinase kinase, CaMKK2, inhibits preadipocyte differentiation
Fumin Lin1, Thomas J Ribar, Anthony R Means
1Department of Pharmacology and Cancer Biology, Duke University Medical School, Durham, North Carolina 27710, USA.
Abstract:
When fed a standard chow diet, CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged. Here, we show that Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is expressed in preadipocytes, where it functions as an AMP-activated protein kinase (AMPK)α kinase. Acute inhibition or deletion of CaMKK2 in preadipocytes enhances their differentiation into mature adipocytes, which can be reversed by 5-aminoimidazole-4-carboxamide ribonucleotide-mediated activation of AMPK. During adipogenesis, CaMKK2 expression is markedly decreased and temporally accompanied by increases in mRNA encoding the early adipogenic genes CCAAT/enhancer binding protein (C/EBP) β and C/EBP δ. Preadipocyte factor 1 has been reported to inhibit adipogenesis by up-regulating sex determining region Y-box 9 (Sox9) expression in preadipocytes and Sox9 suppresses C/EBPβ and C/EBPδ transcription. We show that inhibition of the CaMKK2/AMPK signaling cascade in preadipocytes reduces preadipocyte factor 1 and Sox9 mRNA resulting in accelerated adipogenesis. We conclude that CaMKK2 and AMPK function in a signaling pathway that participates in the regulation of adiposity.
Insights
Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) regulates fat cell differentiation. Inhibiting CaMKK2 in preadipocytes accelerates adipogenesis, impacting overall adiposity.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) null mice exhibit increased adiposity and larger adipocytes on a standard diet.
- Energy balance remains unchanged in these mice, suggesting a specific role for CaMKK2 in adipocyte biology.
Purpose of the Study:
- To investigate the role of CaMKK2 in preadipocyte differentiation and adipogenesis.
- To elucidate the signaling pathway involving CaMKK2 and AMP-activated protein kinase (AMPK) in regulating adiposity.
Main Methods:
- CaMKK2 expression and function were analyzed in preadipocytes.
- Experiments involved acute inhibition or genetic deletion of CaMKK2.
- AMPK activation and its effect on differentiation were assessed.
- Expression levels of key adipogenic genes (C/EBPβ, C/EBPδ, Preadipocyte factor 1, Sox9) were measured.
Main Results:
- CaMKK2 is expressed in preadipocytes and acts as an AMPKα kinase.
- Inhibition or deletion of CaMKK2 enhances preadipocyte differentiation into mature adipocytes.
- Decreased CaMKK2 expression during adipogenesis correlates with increased C/EBPβ and C/EBPδ mRNA.
- Inhibition of the CaMKK2/AMPK pathway reduces Preadipocyte factor 1 and Sox9, accelerating adipogenesis.
Conclusions:
- CaMKK2 and AMPK are integral components of a signaling pathway that regulates adiposity.
- This pathway plays a crucial role in controlling adipocyte differentiation and fat accumulation.
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