Dietary macronutrient composition impacts gene regulation in adipose tissue
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Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomena in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we use the Nutritional Geometry framework to investigate the role of macronutrient composition on metabolic function and gene regulation in adipose tissue. Using ten isocaloric diets that vary systematically in their proportion of energy from fat, protein, and carbohydrates, we find that gene expression and splicing are highly responsive to macronutrient composition, with distinct sets of genes regulated by different macronutrient interactions. Specifically, the expression of many genes associated with Bardet-Biedl syndrome is responsive to dietary fat content. Splicing and expression changes occur in largely separate gene sets, highlighting distinct mechanisms by which dietary composition influences the transcriptome and emphasizing the importance of considering splicing changes to more fully capture the gene regulation response to environmental changes such as diet. Our study provides insight into the gene regulation plasticity of adipose tissue in response to macronutrient composition, beyond the already well-characterized response to caloric intake.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 194 |
| Tidsskrift | Communications Biology |
| Vol/bind | 7 |
| Antal sider | 13 |
| ISSN | 2399-3642 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
This research was funded by a Challenge Programme Grant from the Novo Nordisk Foundation under grant agreement NNF18OC0033754 and the National Institutes of Health (NIH) grants HL128075, U19AI162310 and P30DK020595. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). K. M. F. was supported by an NIH training grant (T32GM007197). We thank all members of the GECKO consortium for their comments and valuable suggestions. We thank the University of Chicago Genomics Facility for their assistance with next-generation sequencing. Tamara Pulpitel and Victoria Pye are acknowledged for their assistance with animal work. In Fig. and Supplementary Fig. , the mouse was sourced from SciDraw and created by Heath Robinson ( https://scidraw.io/drawing/549 , DOI: 10.5281/zenodo.7058520) and the adipose cells in Fig. were adapted from Bioicons (adipocyte-5 icon by Servier). Adipocyte-5 icon by Servier ( https://smart.servier.com/ ) is licensed under CC-BY 3.0 Unported ( https://creativecommons.org/licenses/by/3.0/ ).
Funding Information:
This research was funded by a Challenge Programme Grant from the Novo Nordisk Foundation under grant agreement NNF18OC0033754 and the National Institutes of Health (NIH) grants HL128075, U19AI162310 and P30DK020595. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). K. M. F. was supported by an NIH training grant (T32GM007197). We thank all members of the GECKO consortium for their comments and valuable suggestions. We thank the University of Chicago Genomics Facility for their assistance with next-generation sequencing. Tamara Pulpitel and Victoria Pye are acknowledged for their assistance with animal work. In Fig. 1a and Supplementary Fig. 1, the mouse was sourced from SciDraw and created by Heath Robinson (https://scidraw.io/drawing/549, DOI: 10.5281/zenodo.7058520) and the adipose cells in Fig. 1a were adapted from Bioicons (adipocyte-5 icon by Servier). Adipocyte-5 icon by Servier (https://smart.servier.com/) is licensed under CC-BY 3.0 Unported (https://creativecommons.org/licenses/by/3.0/).
Publisher Copyright:
© The Author(s) 2024.
ID: 385688387