ArticleMolecular metabolism2015
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- A versatile delivery vehicle for cellular oxygen and fuels or metabolic sensor? A review and perspective on the functions of myoglobin.Physiological reviews · 2024Review
- Review
- The adipocyte supersystem of insulin and cAMP signaling.Trends in cell biology · 2023Review
- Activin receptor-like kinase 7 silencing alleviates cardiomyocyte apoptosis, cardiac fibrosis, and dysfunction in diabetic rats.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1.Nature communications · 2021Article
- On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.American journal of physiology. Endocrinology and metabolism · 2021Article
- ALK7 Acts as a Positive Regulator of Macrophage Activation through Down-Regulation of PPARγ Expression.Journal of atherosclerosis and thrombosis · 2021Article
- Control of brown adipose tissue adaptation to nutrient stress by the activin receptor ALK7.eLife · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveObesity is an enormous burden for patients and health systems world-wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor β (TGFβ) receptor Activin receptor-like kinase 7 (Alk7) is highly expressed in adipose tissues and is down-regulated in obese patients. Here, we studied the function of Alk7 in brown adipocytes.
methodsUsing pharmacological and genetic tools, Alk7 signaling pathway and its effects were studied in murine brown adipocytes. Brown adipocyte differentiation and activation was analyzed.
resultsAlk7 is highly upregulated during differentiation of brown adipocytes. Interestingly, Alk7 expression is increased by cGMP/protein kinase G (PKG) signaling, which enhances brown adipocyte differentiation. Activin AB effectively activates Alk7 and SMAD3 signaling. Activation of Alk7 in brown preadipocytes suppresses the master adipogenic transcription factor PPARγ and differentiation. Stimulation of Alk7 during late differentiation of brown adipocytes reduces lipid content and adipogenic marker expression but enhances UCP1 expression.
conclusionsWe found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.
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