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Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction.

ABSTRACT: The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR and perhaps in other adverse states.

SUBMITTER: Cawthorn WP

PROVIDER: S-EPMC4126847 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction.

Cawthorn William P WP Scheller Erica L EL Learman Brian S BS Parlee Sebastian D SD Simon Becky R BR Mori Hiroyuki H Ning Xiaomin X Bree Adam J AJ Schell Benjamin B Broome David T DT Soliman Sandra S SS DelProposto Jenifer L JL Lumeng Carey N CN Mitra Aditi A Pandit Sandeep V SV Gallagher Katherine A KA Miller Joshua D JD Krishnan Venkatesh V Hui Susanta K SK Bredella Miriam A MA Fazeli Pouneh K PK Klibanski Anne A Horowitz Mark C MC Rosen Clifford J CJ MacDougald Ormond A OA

Cell metabolism 20140703 2

The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is ...[more]

PMID: 24998914

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Project description:ObjectivesCaloric restriction (CR) has been shown to slow the aging processes in a number of preclinical studies and reduces expression of aging-associated biomarkers in human trials. We hypothesized that CR would lead to increased incidence of ketosis and that ketosis in CR individuals would alter the aging-protective effects of CR or biomarkers thereof.Design/setting/participantsWe analyzed data from the "Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE, Phase 2)" Public Use Database available at calerie.duke.edu. In this study, non-obese adults between the ages of 21 and 50 were randomized to 25% CR or control (ad lib) diet groups and extensively monitored for two years. Given our focus on the effect of caloric restriction on ketosis, individuals with detectible ketones during the baseline visit (pre-randomization) and those with missing data for ketone testing were excluded from the analysis, leaving 71 control and 117 CR participants.MeasurementsWe analyzed the incidence of ketosis as well as ketosis free survival in control and CR participants and assessed the effect of ketosis on a number of clinical lab values, functional assessments, and participant survey data related to aging biology.ResultsWe report that CR was associated with modestly increased incidence of ketosis (4.4% in CR vs 1.9% in control), though CR-associated changes in T3, VO2, SUMPT-WT (weight normalized composite strength score - peak torque), physical functioning, and general health did not appear to be altered by the presence or absence of ketosis. Additional observations of interest include: 1) striking patterns of biomarker expression changes (MCP-1, TNFα, TGF-β1, GH) in both the control and CR participants between the baseline visit and the 24-month post-randomization visit and 2) pro-growth/anti-inflammatory baseline (pre-randomization) biomarker expression profile in CR individuals that later test ketone positive relative to other CR individuals.ConclusionsCR modestly increases the incidence of ketosis in healthy adults, yet the increase in ketosis in CR patients did not significantly affect the aging-protective effects of CR. However, given the relatively small number of participants who were ketone positive, further investigation in larger study cohorts is still required for definitive conclusions.

Dataset Information

Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction.

Publications

Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction.

Similar Datasets

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