β(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice.
Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple β-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the β(1) isoform in energy homeostasis. First, the 30  min i.v. infusion of norepinephrine (NE) or the β(1) selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the β(1) gene (KO of β(1) adrenergic receptor (β(1)KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, β(1)KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BAT Ucp1 mRNA levels and oxygen consumption. Furthermore, β(1)KO mice exhibited fasting hyperglycemia and more intense glucose intolerance, hypercholesterolemia, and hypertriglyceridemia when placed on the HFD, developing marked non-alcoholic steatohepatitis. In conclusion, the β(1) signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis.
Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, Rua da Consolação, 869 Prédio 16, 1° Andar, 01302-907 São Paulo, Brazil.
Cintia B
CB
Ueta
Gustavo W
GW
Fernandes
Luciane P
LP
Capelo
Tatiane L
TL
Fonseca
Flávia D'Angelo
FD
Maculan
Cecilia H A
CH
Gouveia
Patrícia C
PC
Brum
Marcelo A
MA
Christoffolete
Marcelo S
MS
Aoki
Carmen L
CL
Lancellotti
Brian
B
Kim
Antonio C
AC
Bianco
Miriam O
MO
Ribeiro
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000294:innervation / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D003080:Cold Temperature; D004041:Dietary Fats / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007035:Hypothermia / Q000378:metabolism / Q000503:physiopathology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D000071256:Uncoupling Protein 1
D000316:Adrenergic alpha-Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D001786:Blood Glucose; D004041:Dietary Fats; D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; D018342:Receptors, Adrenergic, beta-1; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D004280:Dobutamine; D009638:Norepinephrine