Adipocyte traits limiting cellular insulin responsiveness and glucose transport
Fryklund, Claes LU ; Neuhaus, Mathis LU
and Stenkula, Karin G
LU
(2023)
In American Journal of Physiology - Endocrinology and Metabolism
325(6).
p.682-687
- Abstract
Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat-depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level. Subcutaneous (inguinal) and visceral (epididymal) adipocytes were isolated from C57BL/6J mice fed either chow or high-fat diet. Cell-size was determined using coulter counter method, glucose uptake and cytosolic volume were assessed using glucose-tracer assays. Total and GLUT4 protein content expression... (More)
Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat-depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level. Subcutaneous (inguinal) and visceral (epididymal) adipocytes were isolated from C57BL/6J mice fed either chow or high-fat diet. Cell-size was determined using coulter counter method, glucose uptake and cytosolic volume were assessed using glucose-tracer assays. Total and GLUT4 protein content expression were determined by western blot. We found that basal glucose uptake per cell was preserved independent of diet or fat depot origin. Insulin-stimulated glucose uptake per cell was sustained in visceral adipocytes but decreased with adipose expansion in subcutaneous adipocytes. In parallel, the cytosolic space and total protein increased proportionally to total cellular volumetric expansion in visceral, but not subcutaneous, adipocytes, while GLUT4 content decreased exclusively in expanding subcutaneous adipocytes. Together, these data support the existence of distinct phenotypic adipocyte traits that could limit cellular insulin responsiveness. Potentially, these characteristics account for fat depot-specific differences related to glucose transport capacity.
(Less)
- author
- Fryklund, Claes
LU
; Neuhaus, Mathis
LU
and Stenkula, Karin G
LU
- organization
- publishing date
- 2023-10-25
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Physiology - Endocrinology and Metabolism
- volume
- 325
- issue
- 6
- pages
- 682 - 687
- publisher
- American Physiological Society
- external identifiers
-
- scopus:85177102505
- pmid:37877798
- ISSN
- 1522-1555
- DOI
- 10.1152/ajpendo.00291.2023
- language
- English
- LU publication?
- yes
- id
- b4288fed-2f88-44fe-8255-f3403bacea1f
- date added to LUP
- 2023-10-25 21:36:07
- date last changed
- 2025-01-25 02:05:24
@article{b4288fed-2f88-44fe-8255-f3403bacea1f,
abstract = {{<p>Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat-depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level. Subcutaneous (inguinal) and visceral (epididymal) adipocytes were isolated from C57BL/6J mice fed either chow or high-fat diet. Cell-size was determined using coulter counter method, glucose uptake and cytosolic volume were assessed using glucose-tracer assays. Total and GLUT4 protein content expression were determined by western blot. We found that basal glucose uptake per cell was preserved independent of diet or fat depot origin. Insulin-stimulated glucose uptake per cell was sustained in visceral adipocytes but decreased with adipose expansion in subcutaneous adipocytes. In parallel, the cytosolic space and total protein increased proportionally to total cellular volumetric expansion in visceral, but not subcutaneous, adipocytes, while GLUT4 content decreased exclusively in expanding subcutaneous adipocytes. Together, these data support the existence of distinct phenotypic adipocyte traits that could limit cellular insulin responsiveness. Potentially, these characteristics account for fat depot-specific differences related to glucose transport capacity.</p>}},
author = {{Fryklund, Claes and Neuhaus, Mathis and Stenkula, Karin G}},
issn = {{1522-1555}},
language = {{eng}},
month = {{10}},
number = {{6}},
pages = {{682--687}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology - Endocrinology and Metabolism}},
title = {{Adipocyte traits limiting cellular insulin responsiveness and glucose transport}},
url = {{http://dx.doi.org/10.1152/ajpendo.00291.2023}},
doi = {{10.1152/ajpendo.00291.2023}},
volume = {{325}},
year = {{2023}},
}