Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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 orcid ; 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)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
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
2022-09-17 04:07:36
@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}},
}