Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features
Axling, Ulrika LU ; Cavalera, Michele LU ; Degerman, Eva LU
; Gåfvels, Mats
LU
; Eggertsen, Gösta
and Holm, Cecilia
LU
(2020)
In Adipocyte
9(1).
p.587-599
- Abstract
The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using the Cyp8b1−/- mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool. Cyp8b1−/- mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output in Cyp8b1−/ mice. Indirect calorimetry measurements demonstrated increased energy expenditure in Cyp8b1−/- mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower in Cyp8b1−/- mice. Intravenous glucose tolerance... (More)
The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using the Cyp8b1−/- mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool. Cyp8b1−/- mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output in Cyp8b1−/ mice. Indirect calorimetry measurements demonstrated increased energy expenditure in Cyp8b1−/- mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower in Cyp8b1−/- mice. Intravenous glucose tolerance tests, as well as static incubations of isolated islets, showed no difference between the groups, whereas insulin tolerance tests demonstrated improved insulin sensitivity in Cyp8b1−/- mice. The genes encoding mitochondrial transcription factor A (TFAM) and type 2-iodothyronine deiodinase were upregulated in brown adipose tissue of Cyp8b1/- mice and Western blot analyses showed increased abundance of TFAM, and a trend towards increased abundance of UCP1. The upregulation of TFAM and UCP1 was accompanied by increased mitochondrial density, as shown by transmission electron microscopy. White adipocytes of Cyp8b1−/- mice exhibited increased responsiveness to both catecholamines and insulin in lipolysis experiments and increased insulin-stimulated lipogenesis. In conclusion, increased energy expenditure, mitochondrial density of brown adipocytes and faecal energy output may all contribute to the protection against diet-induced obesity of Cyp8b1−/- mice. Enhanced insulin sensitivity of Cyp8b1−/- mice is accompanied by increased hormonal responsiveness of white adipocytes.
(Less)
- author
- Axling, Ulrika
LU
; Cavalera, Michele
LU
; Degerman, Eva
LU
; Gåfvels, Mats
LU
; Eggertsen, Gösta
and Holm, Cecilia
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bile acids, brown adipocytes, energy expenditure, glucose tolerance, insulin secretion, insulin sensitivity, lipogenesis, lipolysis, white adipocytes
- in
- Adipocyte
- volume
- 9
- issue
- 1
- pages
- 13 pages
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:85091892579
- pmid:33016185
- ISSN
- 2162-3945
- DOI
- 10.1080/21623945.2020.1827519
- language
- English
- LU publication?
- yes
- id
- 4e5cdad0-317f-42c3-8bf9-40ccca3334a1
- date added to LUP
- 2020-11-19 11:48:00
- date last changed
- 2024-04-03 17:42:21
@article{4e5cdad0-317f-42c3-8bf9-40ccca3334a1,
abstract = {{<p>The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using the Cyp8b1<sup>−/-</sup> mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool. Cyp8b1<sup>−/-</sup> mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output in Cyp8b1<sup>−/</sup> mice. Indirect calorimetry measurements demonstrated increased energy expenditure in Cyp8b1<sup>−/-</sup> mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower in Cyp8b1<sup>−/-</sup> mice. Intravenous glucose tolerance tests, as well as static incubations of isolated islets, showed no difference between the groups, whereas insulin tolerance tests demonstrated improved insulin sensitivity in Cyp8b1<sup>−/-</sup> mice. The genes encoding mitochondrial transcription factor A (TFAM) and type 2-iodothyronine deiodinase were upregulated in brown adipose tissue of Cyp8b1<sup>/-</sup> mice and Western blot analyses showed increased abundance of TFAM, and a trend towards increased abundance of UCP1. The upregulation of TFAM and UCP1 was accompanied by increased mitochondrial density, as shown by transmission electron microscopy. White adipocytes of Cyp8b1<sup>−/-</sup> mice exhibited increased responsiveness to both catecholamines and insulin in lipolysis experiments and increased insulin-stimulated lipogenesis. In conclusion, increased energy expenditure, mitochondrial density of brown adipocytes and faecal energy output may all contribute to the protection against diet-induced obesity of Cyp8b1<sup>−/-</sup> mice. Enhanced insulin sensitivity of Cyp8b1<sup>−/-</sup> mice is accompanied by increased hormonal responsiveness of white adipocytes.</p>}},
author = {{Axling, Ulrika and Cavalera, Michele and Degerman, Eva and Gåfvels, Mats and Eggertsen, Gösta and Holm, Cecilia}},
issn = {{2162-3945}},
keywords = {{Bile acids; brown adipocytes; energy expenditure; glucose tolerance; insulin secretion; insulin sensitivity; lipogenesis; lipolysis; white adipocytes}},
language = {{eng}},
number = {{1}},
pages = {{587--599}},
publisher = {{Taylor & Francis}},
series = {{Adipocyte}},
title = {{Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features}},
url = {{http://dx.doi.org/10.1080/21623945.2020.1827519}},
doi = {{10.1080/21623945.2020.1827519}},
volume = {{9}},
year = {{2020}},
}