Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 13;18(4):e0283276.
doi: 10.1371/journal.pone.0283276. eCollection 2023.

CD36 regulates substrates utilisation in brown adipose tissue of spontaneously hypertensive rats: In vitro study

Jan Silhavy  1 , Petr Mlejnek  1 , Miroslava Šimáková  1 , Irena Marková  2 , Hana Malínská  2 , Martina Hüttl  2 , Ludmila Kazdová  2 , Dmitry Kazantsev  3   4 , Massimiliano Mancini  5 , Jiří Novotný  3 , Michal Pravenec  1
Affiliations

CD36 regulates substrates utilisation in brown adipose tissue of spontaneously hypertensive rats: In vitro study

Jan Silhavy et al. PLoS One. .

Abstract

Thermogenesis in brown adipose tissue (BAT) uses intracellular triglycerides, circulating free fatty acids and glucose as the main substrates. The objective of the current study was to analyse the role of CD36 fatty acid translocase in regulation of glucose and fatty acid utilisation in BAT. BAT isolated from spontaneously hypertensive rat (SHR) with mutant Cd36 gene and SHR-Cd36 transgenic rats with wild type variant was incubated in media containing labeled glucose and palmitate to measure substrate incorporation and oxidation. SHR-Cd36 versus SHR rats showed significantly increased glucose incorporation into intracellular lipids associated with reduced glycogen synthase kinase 3β (GSK-3β) protein expression and phosphorylation and increased oxidation of exogenous palmitate. It can be concluded that CD36 enhances glucose transport for lipogenesis in BAT by suppressing GSK-3β and promotes direct palmitate oxidation.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Effects of Cd36 on substrate utilisation in BAT.
A. Ex vivo glucose and palmitate incorporation into BAT lipids in SHR-Cd36 transgenic versus SHR rats. B. Ex vivo glucose and palmitate oxidation in BAT from SHR-Cd36 transgenic versus SHR rats. Two-way ANOVA results: P values of statistical significance for effects strain (Cd36 genotype), type of incubation media (glucose/palmitate) and strain x substrate interaction. For pairwise multiple comparison procedures Holm Sidak testing was used. * and *** denote P<0.05 and P<0.001, respectively.
Fig 2
Fig 2. Effect of Cd36 on expression and phosphorylation of key components of the insulin signalling pathway.
Samples of BAT isolated from SHR and SHR-Cd36 were incubated in Krebs-Ringer bicarbonate buffer with glucose alone or together with palmitate, then homogenised and subjected to gel electrophoresis and Western blotting as described in Methods. Immunoblots shown are representative of six experiments (A). Signal intensities corresponding to detected proteins were quantified by densitometric analysis and normalised to total protein determined by Ponceau staining (B). *, **, and *** denote P<0.05, P<0.01, and P<0.001 significant differences.
Fig 3
Fig 3. Effect of Cd36 on expression of genes involved in insulin signalling pathway and glucose metabolism.
Two-way ANOVA results: P values of statistical significance for effects strain (Cd36 genotype), type of incubation media (glucose/palmitate) and strain x substrate interaction. For pairwise multiple comparison procedures Holm Sidak testing was used. *, **, and *** denote P<0.05, P<0.01, and P<0.001 significant differences.
Fig 4
Fig 4. Capillary number in BAT was significantly increased in SHR-Cd36 versus SHR rats.
* denotes P<0.003.
See this image and copyright information in PMC

References

    1. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al.. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011;17: 200–205. doi: 10.1038/nm.2297 - DOI - PubMed
    1. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. PLoS One. 2011;6: e17247. doi: 10.1371/journal.pone.0017247 - DOI - PMC - PubMed
    1. Virtanen KA. The rediscovery of BAT in adult humans using imaging. Best Pract Res Clin Endocrinol Metab. 2016;30: 471–477. doi: 10.1016/j.beem.2016.09.001 - DOI - PubMed
    1. Pravenec M, Zídek V, Mlejnek P, Landa V, Mlejnek P, Šilhavý J, et al.. Systems analysis of brown adipose tissue function in recombinant inbred rats. Physiol Genomics. 2018;50: 52–66. - PMC - PubMed
    1. Glazier AM, Scott J, Aitman TJ. Molecular basis of the Cd36 chromosomal deletion underlying SHR defects in insulin action and fatty acid metabolism. Mamm Genome. 2002;13: 108–113. doi: 10.1007/s00335-001-2132-9 - DOI - PubMed

Publication types