title: β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice.
abstract: Catecholamines acting through β-adrenergic receptors (β(1)-, β(2)-, β(3)-AR subtypes) modulate important biological responses in various tissues. Our previous studies suggest a role for increased hepatic β-AR-mediated signaling during aging as a mediator of hepatic steatosis, liver glucose output, and insulin resistance in rodents. In the current study, we have utilized β(2)-AR knockout (KO) and wildtype (WT) control mice to define further the role of β(2)-AR signaling during aging on lipid and glucose metabolism. Our results demonstrate for the first time that age-related increases in hepatic triglyceride accumulation and body weight are attenuated upon β(2)-AR ablation. Although no differences in plasma triglyceride, non-esterified fatty acids or insulin levels were detected between old WT and KO animals, an age-associated increase in hepatic expression of lipid homeostasis regulator Cidea was significantly reduced in old KO mice. Interestingly, we also observed a shift from reduced glucose tolerance in young adult KO animals to significantly improved glucose tolerance in old KO when compared to age-matched WT mice. These results provide evidence for an important role played by β(2)-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β(2)-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β(2)-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population.
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: shiy@uthscsa.edu.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: shuz2@uthscsa.edu.
authors.forename: Zhen-Ju
authors.initials: ZJ
authors.lastname: Shu
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: xue@uthscsa.edu.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xue
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: yeh@uthscsa.edu.
authors.forename: Chih-Ko
authors.initials: CK
authors.lastname: Yeh
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA; Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: katz@uthscsa.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Katz
authors.affiliation: Geriatric Research, Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, TX 78229, USA. Electronic address: Amrita.Kamat@va.gov.
authors.forename: Amrita
authors.initials: A
authors.lastname: Kamat
mesh_terms: D000375:Aging; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D007328:Insulin; D018343:Receptors, Adrenergic, beta-2; D014280:Triglycerides; D005947:Glucose
keywords: Cide; Hepatocytes; Lipid; Metabolism; Nonalcoholic fatty liver disease; Triglycerides