CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway. 2023

Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, California 95616, USA; Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul 08826, South Korea.

Cystic fibrosis (CF) is characterized by reduced growth and lower body weight, which are multifactorial. CF mouse models lack key disease characteristics that predispose to a negative energy balance, such as pulmonary infections or exocrine pancreatic insufficiency, and yet they still exhibit a growth defect and an abnormally increased energy expenditure. Whether adipocyte thermogenesis contributes to the elevated resting energy expenditure in CF mice is unknown. We examined the expression of CFTR in thermogenic brown adipose tissue (BAT) and investigated a functional role for CFTR using BAT-specific CFTR null mice (CFTRBATKO). The CFTR protein is expressed in mouse BAT at levels comparable to those in the lungs. BAT-specific inactivation of CFTR in mice increases whole-body energy expenditure associated with sympathetic stimulation by cold exposure. Weight gain on a high-fat diet is attenuated in these mice. However, CFTR-deficient brown adipocytes themselves have impaired, rather than enhanced, thermogenic responses. These cells feature decreased lipolysis and blunted activation of the cAMP/PKA signaling pathway in response to adrenergic stimulation. This suggests that compensatory heat production in other tissues likely accounts for the increased systemic energy expenditure seen in CFTRBATKO mice. Our data reveal a new role for CFTR in the regulation of adipocyte thermogenesis.

UI MeSH Term Description Entries
D003550 Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION. Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D052437 Adipocytes, Brown Fat cells with dark coloration due to the densely packed MITOCHONDRIA. They contain numerous small lipid droplets or vacuoles. Their stored lipids can be converted directly to energy as heat by the mitochondria. Brown Adipocytes,Brown Fat Cells,Adipocyte, Brown,Brown Adipocyte,Brown Fat Cell,Cell, Brown Fat,Cells, Brown Fat,Fat Cell, Brown,Fat Cells, Brown
D017868 Cyclic AMP-Dependent Protein Kinases A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition. Adenosine Cyclic Monophosphate-Dependent Protein Kinases,Protein Kinase A,cAMP Protein Kinase,cAMP-Dependent Protein Kinases,Cyclic AMP-Dependent Protein Kinase,cAMP-Dependent Protein Kinase,Adenosine Cyclic Monophosphate Dependent Protein Kinases,Cyclic AMP Dependent Protein Kinase,Cyclic AMP Dependent Protein Kinases,Protein Kinase, cAMP,Protein Kinase, cAMP-Dependent,Protein Kinases, cAMP-Dependent,cAMP Dependent Protein Kinase,cAMP Dependent Protein Kinases
D019005 Cystic Fibrosis Transmembrane Conductance Regulator A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8) CFTR Protein,Chloride channels, ATP-gated CFTR,Chloride channels, ATP gated CFTR,Protein, CFTR
D022722 Thermogenesis The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and SHIVERING are examples of thermogenesis in MAMMALS. Heat Production,Adaptive Thermogenesis,Facultative Thermogenesis,Nonshivering Thermogenesis,Production, Heat,Thermogeneses,Thermogenesis, Adaptive,Thermogenesis, Facultative,Thermogenesis, Nonshivering

Related Publications

Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
April 2024, Biochemical and biophysical research communications,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
October 2010, Acta pharmacologica Sinica,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
June 2018, Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
September 2019, Journal of molecular cell biology,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
May 2024, JCI insight,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
November 2018, Molecular and cellular endocrinology,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
August 2019, Nature metabolism,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
September 2017, Oncotarget,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
January 2022, The Journal of endocrinology,
Kyung-Mi Choi, and Sung-Hee Cho, and Jung Hak Kim, and Ae-Rhee Lilian Kim, and Xiangmudong Kong, and John C Yoon
June 2020, Journal of cellular and molecular medicine,
Copied contents to your clipboard!