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Sex-and depot-specific differences in cellular insulin responsiveness during adipose expansion

Neuhaus, Mathis LU orcid and Stenkula, Karin LU (2025) In Life Sciences 375.
Abstract
Aims
Adipose tissue distribution, metabolism, and expansion capacity exhibit notable sex- and depot-specific differences. Herein, we monitored adipocyte traits related to insulin responsiveness and glucose transport during adipose expansion in visceral and subcutaneous fat from male and female mice.
Material and methods
Adipocytes were isolated from perigonadal and inguinal adipose tissue of chow-fed female and male C57Bl6/J mice and assessed for adipocyte size distribution using a coulter counter; glucose uptake and cytosolic volume were measured using glucose tracer assays. GLUT1, GLUT4, and IRS-1 protein levels were accessed by western blot. Pharmacological inhibition (BAY876) of GLUT1 and GLUT4 was used to resolve their... (More)
Aims
Adipose tissue distribution, metabolism, and expansion capacity exhibit notable sex- and depot-specific differences. Herein, we monitored adipocyte traits related to insulin responsiveness and glucose transport during adipose expansion in visceral and subcutaneous fat from male and female mice.
Material and methods
Adipocytes were isolated from perigonadal and inguinal adipose tissue of chow-fed female and male C57Bl6/J mice and assessed for adipocyte size distribution using a coulter counter; glucose uptake and cytosolic volume were measured using glucose tracer assays. GLUT1, GLUT4, and IRS-1 protein levels were accessed by western blot. Pharmacological inhibition (BAY876) of GLUT1 and GLUT4 was used to resolve their respective contribution to cellular glucose transport.
Key findings
Independent of adiposity or sex, visceral adipocytes were larger and displayed higher glucose transport, cytosolic volume, and GLUT4 expression than subcutaneous adipocytes. Pharmacological inhibition confirmed that GLUT1 contributes to <10 % of adipocyte glucose uptake, while GLUT4 facilitates most of both basal and insulin-stimulated glucose uptake. Females showed significantly higher basal and insulin-stimulated glucose transport, higher cytosolic volume, and greater GLUT4 and IRS-1 protein levels than males in both adipose depots. Interestingly, insulin responsiveness was preserved in female subcutaneous adipocytes but deteriorated in subcutaneous male adipocytes during adipose expansion.
Significance
The improved insulin responsiveness, increased glucose transport, and higher levels of GLUT4 and IRS-1 in adipocytes might protect females from the adverse systemic effects linked to obesity. Insulin responsiveness was preserved in female subcutaneous adipocytes during adipose tissue expansion, which could contribute to the reduced risk of systemic insulin resistance in females. (Less)
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author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Life Sciences
volume
375
article number
123743
publisher
Elsevier
ISSN
1879-0631
DOI
10.1016/j.lfs.2025.123743
language
English
LU publication?
yes
id
8a7b150f-e0f1-4241-9111-a580db1ef080
date added to LUP
2025-05-21 12:57:19
date last changed
2025-05-22 16:27:02
@article{8a7b150f-e0f1-4241-9111-a580db1ef080,
  abstract     = {{Aims<br/>Adipose tissue distribution, metabolism, and expansion capacity exhibit notable sex- and depot-specific differences. Herein, we monitored adipocyte traits related to insulin responsiveness and glucose transport during adipose expansion in visceral and subcutaneous fat from male and female mice.<br/>Material and methods<br/>Adipocytes were isolated from perigonadal and inguinal adipose tissue of chow-fed female and male C57Bl6/J mice and assessed for adipocyte size distribution using a coulter counter; glucose uptake and cytosolic volume were measured using glucose tracer assays. GLUT1, GLUT4, and IRS-1 protein levels were accessed by western blot. Pharmacological inhibition (BAY876) of GLUT1 and GLUT4 was used to resolve their respective contribution to cellular glucose transport.<br/>Key findings<br/>Independent of adiposity or sex, visceral adipocytes were larger and displayed higher glucose transport, cytosolic volume, and GLUT4 expression than subcutaneous adipocytes. Pharmacological inhibition confirmed that GLUT1 contributes to &lt;10 % of adipocyte glucose uptake, while GLUT4 facilitates most of both basal and insulin-stimulated glucose uptake. Females showed significantly higher basal and insulin-stimulated glucose transport, higher cytosolic volume, and greater GLUT4 and IRS-1 protein levels than males in both adipose depots. Interestingly, insulin responsiveness was preserved in female subcutaneous adipocytes but deteriorated in subcutaneous male adipocytes during adipose expansion.<br/>Significance<br/>The improved insulin responsiveness, increased glucose transport, and higher levels of GLUT4 and IRS-1 in adipocytes might protect females from the adverse systemic effects linked to obesity. Insulin responsiveness was preserved in female subcutaneous adipocytes during adipose tissue expansion, which could contribute to the reduced risk of systemic insulin resistance in females.}},
  author       = {{Neuhaus, Mathis and Stenkula, Karin}},
  issn         = {{1879-0631}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Life Sciences}},
  title        = {{Sex-and depot-specific differences in cellular insulin responsiveness during adipose expansion}},
  url          = {{http://dx.doi.org/10.1016/j.lfs.2025.123743}},
  doi          = {{10.1016/j.lfs.2025.123743}},
  volume       = {{375}},
  year         = {{2025}},
}