Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Cecilia Holm

Professor

Default user image.

Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features

Author

  • Ulrika Axling
  • Michele Cavalera
  • Eva Degerman
  • Mats Gåfvels
  • Gösta Eggertsen
  • Cecilia Holm

Summary, in English

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.

Department/s

  • Molecular Endocrinology
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • Insulin Signal Transduction
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Department of Laboratory Medicine

Publishing year

2020

Language

English

Pages

587-599

Publication/Series

Adipocyte

Volume

9

Issue

1

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Endocrinology and Diabetes

Keywords

  • Bile acids
  • brown adipocytes
  • energy expenditure
  • glucose tolerance
  • insulin secretion
  • insulin sensitivity
  • lipogenesis
  • lipolysis
  • white adipocytes

Status

Published

Research group

  • Molecular Endocrinology
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 2162-3945