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Publication
Loss of CREB Coactivator CRTC1 in SF1 Cells Leads to Hyperphagia and Obesity by
High-fat Diet But Not Normal Chow Diet.
Authors Matsumura S, Ishikawa F, Sasaki T, Terkelsen MK, Ravnskjaer K, Jinno T, Tanaka
J, Goto T, Inoue K
Submitted By Submitted Externally on 1/10/2022
Status Published
Journal Endocrinology
Year 2021
Date Published 9/1/2021
Volume : Pages 162 : Not Specified
PubMed Reference 33846709
Abstract Cyclic adenosine monophosphate responsive element-binding protein-1-regulated
transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that
translocates to the nucleus in response to cyclic adenosine monophosphate.
Whole-body knockdown of Crtc1 causes obesity, resulting in increased food intake
and reduced energy expenditure. CRTC1 is highly expressed in the brain;
therefore, it might play an important role in energy metabolism via the neuronal
pathway. However, the precise mechanism by which CRTC1 regulates energy
metabolism remains unknown. Here, we showed that mice lacking CRTC1,
specifically in steroidogenic factor-1 expressing cells (SF1 cells), were
sensitive to high-fat diet (HFD)-induced obesity, exhibiting hyperphagia and
increased body weight gain. The loss of CRTC1 in SF1 cells impaired glucose
metabolism. Unlike whole-body CRTC1 knockout mice, SF1 cell-specific CRTC1
deletion did not affect body weight gain or food intake in normal chow feeding.
Thus, CRTC1 in SF1 cells is required for normal appetite regulation in HFD-fed
mice. CRTC1 is primarily expressed in the brain. Within the hypothalamus, which
plays an important role for appetite regulation, SF1 cells are only found in
ventromedial hypothalamus. RNA sequencing analysis of microdissected
ventromedial hypothalamus samples revealed that the loss of CRTC1 significantly
changed the expression levels of certain genes. Our results revealed the
important protective role of CRTC1 in SF1 cells against dietary metabolic
imbalance.




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