Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids.
Adipose tissue expansion has been associated with system-wide metabolic dysfunction and increased vulnerability to diabetes, cancer, and cardiovascular disease. A reduction in adiposity is a hallmark of caloric restriction (CR), an intervention that extends longevity and delays the onset of these same age-related conditions. Despite these parallels, the role of adipose tissue in coordinating the metabolism of aging is poorly defined. Here, we show that adipose tissue metabolism and secretory profiles change with age and are responsive to CR. We conducted a cross-sectional study of CR in adult, late-middle-aged, and advanced-aged mice. Adiposity and the relationship between adiposity and circulating levels of the adipose-derived peptide hormone adiponectin were age-sensitive. CR impacted adiposity but only levels of the high molecular weight isoform of adiponectin responded to CR. Activators of metabolism including PGC-1a, SIRT1, and NAMPT were differentially expressed with CR in adipose tissues. Although age had a significant impact on NAD metabolism, as detected by biochemical assay and multiphoton imaging, the impact of CR was subtle and related to differences in reliance on oxidative metabolism. The impact of age on circulating lipids was limited to composition of circulating phospholipids. In contrast, the impact of CR was detected in all lipid classes regardless of age, suggesting a profound difference in lipid metabolism. These data demonstrate that aspects of adipose tissue metabolism are life phase specific and that CR is associated with a distinct metabolic state, suggesting that adipose tissue signaling presents a suitable target for interventions to delay aging.
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.|Department of Nutritional Sciences, University of Wisconsin Madison, Madison, WI, 53706, USA.
Karl N
KN
Miller
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.
Maggie S
MS
Burhans
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.
Josef P
JP
Clark
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.
Porsha R
PR
Howell
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.
Michael A
MA
Polewski
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.
Tyler M
TM
DeMuth
Laboratory for Optical and Computational Instrumentation, University of Wisconsin Madison, Madison, WI, 53706, USA.
Kevin W
KW
Eliceiri
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, 53705, USA.
Mary J
MJ
Lindstrom
Department of Nutritional Sciences, University of Wisconsin Madison, Madison, WI, 53706, USA.|Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA.
James M
JM
Ntambi
Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, 53706, USA.|Laboratory for Optical and Computational Instrumentation, University of Wisconsin Madison, Madison, WI, 53706, USA.|GRECC, William S. Middleton Memorial Veterans Hospital, Madison, WI, 53705, USA.
Rozalyn M
RM
Anderson
D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008055:Lipids / Q000097:blood* / Q000145:classification; D008297:Male; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; C499919:Adipoq protein, mouse; D016207:Cytokines; D008055:Lipids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D020033:Protein Isoforms; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
NAD metabolism; adiponectin; adipose tissue; aging; caloric restriction; fatty acids