Differential expression of immunoregulatory cytokines in adipose tissue and liver in response to high fat and high sugar diets in female mice

Juliane Weiner; Sebastian Dommel; Claudia Gebhardt; Martha Hanschkow; Yulia Popkova; Kerstin Krause; Nora Klöting; Matthias Blüher; Jürgen Schiller; John T Heiker

doi:10.3389/fnut.2023.1275160

Differential expression of immunoregulatory cytokines in adipose tissue and liver in response to high fat and high sugar diets in female mice

Front Nutr. 2023 Nov 3:10:1275160. doi: 10.3389/fnut.2023.1275160. eCollection 2023.

Authors

Juliane Weiner¹, Sebastian Dommel², Claudia Gebhardt², Martha Hanschkow³, Yulia Popkova³, Kerstin Krause^{1

4}, Nora Klöting², Matthias Blüher^{1

2}, Jürgen Schiller³, John T Heiker^{2

5}

Affiliations

¹ Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
² Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
³ Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Leipzig, Germany.
⁴ Deutsches Zentrum für Diabetesforschung e.V., Neuherberg, Germany.
⁵ Institute for Biochemistry, Faculty of Life Sciences, University of Leipzig, Leipzig, Germany.

Abstract

A comprehensive understanding of how dietary components impact immunoregulatory gene expression in adipose tissue (AT) and liver, and their respective contributions to metabolic health in mice, remains limited. The current study aimed to investigate the metabolic consequences of a high-sucrose diet (HSD) and a high-fat diet (HFD) in female mice with a focus on differential lipid- and sucrose-induced changes in immunoregulatory gene expression in AT and liver. Female C57BL/6 J mice were fed a purified and macronutrient matched high fat, high sugar, or control diets for 12 weeks. Mice were extensively phenotyped, including glucose and insulin tolerance tests, adipose and liver gene and protein expression analysis by qPCR and Western blot, tissue lipid analyses, as well as histological analyses. Compared to the control diet, HSD- and HFD-fed mice had significantly higher body weights, with pronounced obesity along with glucose intolerance and insulin resistance only in HFD-fed mice. HSD-fed mice exhibited an intermediate phenotype, with mild metabolic deterioration at the end of the study. AT lipid composition was significantly altered by both diets, and inflammatory gene expression was only significantly induced in HFD-fed mice. In the liver however, histological analysis revealed that both HSD- and HFD-fed mice had pronounced ectopic lipid deposition indicating hepatic steatosis, but more pronounced in HSD-fed mice. This was in line with significant induction of pro-inflammatory gene expression specifically in livers of HSD-fed mice. Overall, our findings suggest that HFD consumption in female mice induces more profound inflammation in AT with pronounced deterioration of metabolic health, whereas HSD induced more pronounced hepatic steatosis and inflammation without yet affecting glucose metabolism.

Keywords: adipose tissue; high fat diet; high sugar diet; inflammation; lipid profile; nutrient; nutrition; obesity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by grants of the Deutsche Forschungsgemeinschaft SFB1052 “Obesity Mechanisms” (Project number: 209933838, B1 MB, B4 NK, B12 KK, C7 JTH, Z3 JS).