p27Kip1 Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice
Colon-Mesa, Ignacio ; Sainz, Neira ; Corrales, Patricia ; Collantes, María ; Kaldis, Philipp LU
; Martinez, José Alfredo
; Medina-Gómez, Gema
; Moreno-Aliaga, María Jesús
and Escoté, Xavier
(2023)
In International Journal of Molecular Sciences
24(3).
- Abstract
The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27−/−) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by... (More)
The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27−/−) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27−/− mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27−/− mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27−/− HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27−/− HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.
(Less)
- author
- Colon-Mesa, Ignacio
; Sainz, Neira
; Corrales, Patricia
; Collantes, María
; Kaldis, Philipp
LU
; Martinez, José Alfredo
; Medina-Gómez, Gema
; Moreno-Aliaga, María Jesús
and Escoté, Xavier
- organization
- publishing date
- 2023-01-31
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- brown adipose tissue, insulin resistance, obesity, p27
- in
- International Journal of Molecular Sciences
- volume
- 24
- issue
- 3
- article number
- 2664
- pages
- 17 pages
- publisher
- MDPI AG
- external identifiers
-
- scopus:85147996165
- pmid:36768986
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms24032664
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This work was mainly supported by a grant from the Navarra Government-Centros Tecnológicos 0011-1383-2019-000005 (PC056-057) ALZOBIN. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute (CB12/03/30002) is also acknowledged. X.E. is financially supported by the Catalan Government through the funding grant ACCIÓ-Eurecat and by the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation under the grant agreement TECNOMIFOOD project (CER-20191010). Grant PID2020-116875RB-I00 (MICINN/AEI/FEDER, EU) to G.M.-G. and Grant PID2019-106982RB-I00 (MICINN/AEI/FEDER, EU) to M.J.M-A. are also acknowledged. I.C.-M. was supported by a predoctoral grant from the Center for Nutrition Research (University of Navarra). Publisher Copyright: © 2023 by the authors.
- id
- c5cbfb9a-9273-4528-ad95-1a3ac96cf12b
- date added to LUP
- 2023-02-28 10:03:51
- date last changed
- 2024-05-16 11:09:57
@article{c5cbfb9a-9273-4528-ad95-1a3ac96cf12b,
abstract = {{<p>The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27<sup>−/−</sup>) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>FDG) uptake with microPET. p27<sup>−/−</sup> mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27<sup>−/−</sup> mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27<sup>−/−</sup> HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27<sup>−/−</sup> HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT <sup>18</sup>FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.</p>}},
author = {{Colon-Mesa, Ignacio and Sainz, Neira and Corrales, Patricia and Collantes, María and Kaldis, Philipp and Martinez, José Alfredo and Medina-Gómez, Gema and Moreno-Aliaga, María Jesús and Escoté, Xavier}},
issn = {{1661-6596}},
keywords = {{brown adipose tissue; insulin resistance; obesity; p27}},
language = {{eng}},
month = {{01}},
number = {{3}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{p27<sup>Kip1</sup> Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice}},
url = {{http://dx.doi.org/10.3390/ijms24032664}},
doi = {{10.3390/ijms24032664}},
volume = {{24}},
year = {{2023}},
}