Cited by 25Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesLipid metabolism and biosynthesis

Cell-autonomous heterogeneity of nutrient uptake in white adipose tissue of rhesus macaques

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Varlamov, Oleg, Chu, Michael, Cornea, Anda, Sampath, Harini, Roberts, Charles T.·2015·Endocrinology

Abstract

Phenotypic diversity may play an adaptive role by providing graded biological responses to fluctuations in environmental stimuli. We used single-cell imaging of the metabolizable fluorescent fatty acid analog 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-C12 and fluorescent 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) to explore cellular heterogeneity in nutrient uptake in white adipose tissue (WAT) explants of rhesus macaques. Surprisingly, WAT displayed a striking cell size-independent mosaic pattern, in that adjacent adipocytes varied with respect to insulin-stimulated BODIPY-C12 and 2-NBDG uptake. Relative free fatty acid (FFA) transport activity correlated with the cellular levels of FFA transporter protein-1 and the scavenger receptor CD36 in individual adipocytes. In vitro incubation of WAT explants for 24 hours caused partial desynchronization of cellular responses, suggesting that adipocytes may slowly alter their differential nutrient uptake activity. In vitro-differentiated human adipocytes also exhibited a mosaic pattern of BODIPY-C12 uptake. WAT from animals containing a homogeneous population of large adipocytes was nonmosaic, in that every adipocyte exhibited a similar level of BODIPY-C12 fluorescence, suggesting that the development of obesity is associated with the loss of heterogeneity in WAT. Hence, for the first time, we demonstrate an intrinsic heterogeneity in FFA and glucose transport activity in WAT.

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Authors
Varlamov, O., Chu, M., Cornea, A., Sampath, H., & Roberts, C. T.
Affiliations
  • Oregon National Primate Research Center (US)
  • Oregon Health & Science University (US)
Corresponding author
Varlamov, Oleg
Venue
Endocrinology
Published
2015-01
Volume
156
Issue
1
Pages
80-89
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2029387575
Cited by
25
References
4
Citations by year
2025: 1 · 2024: 6 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 2 · 2015: 2
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (HD071836, DK100640, OD-011092, P51OD011092, U42OD010426)
  • Oregon National Primate Research Center (P51OD011092, P50 HD071836, OD011092)
  • National Institute on Aging (R21AG047543)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K99DK100640)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD071836)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
white adipose tissue, adipocyte heterogeneity, free fatty acid uptake, glucose uptake, insulin signaling, CD36, 2-NBDG, rhesus monkeys, obesity, adipocyte size, single-cell imaging
MeSH terms
Animals, Biological Transport, Female, Fluorescent Dyes, Humans, Macaca mulatta, Staining and Labeling, Tissue Culture Techniques, Adipose Tissue, White

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