open access publication

Preprint, 2023

Impact of dietary macronutrient composition on gene regulation in adipose tissue

Research Square, 10.21203/


Farris, Kathryn M 0000-0002-7599-8050 [1] Senior, Alistair Mcnair 0000-0001-9805-7280 [2] Sobreira, Débora Rodrigues 0000-0002-2232-3922 [1] Ingerslev, Lars Roed 0000-0002-4164-7690 [3] Barrès, Romain Emmanuel 0000-0002-0158-519X [3] Simpson, Stephen James 0000-0003-0256-7687 [2] Crean, Angela Jane 0000-0003-2605-6435 Nobrega, Marcelo Aguiar 0000-0002-2134-9661 [1]


  1. [1] University of Chicago
  2. [NORA names: United States; America, North; OECD];
  3. [2] The University of Sydney
  4. [NORA names: Australia; Oceania; OECD];
  5. [3] University of Copenhagen
  6. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]


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 phenomenon in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we used 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 found 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 was responsive to dietary fat content. Splicing and expression changes occurred 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.


Bardet-Biedl syndrome, adipose, adipose tissue, caloric intake, carbohydrate, changes, components, composition, content, diet, dietary composition, dietary fat content, dietary macronutrient composition, energy, energy intake, environmental changes, expression, expression changes, factors, fat, fat content, framework, function, gene expression, gene regulation, gene sets, genes, geometry framework, health, impact, impact of caloric intake, impact of dietary macronutrient composition, influence, influence metabolic health, intake, interaction, isocaloric diets, lifestyle, lifestyle components, macronutrient composition, macronutrient interactions, mechanism, metabolic functions, metabolic health, nutrition, nutritional geometry framework, parameters, phenomenon, physiological phenomena, plasticity of adipose tissue, proportion, proportion of energy, protein, regulation, response, response to caloric intake, response to environmental changes, sets, sets of genes, splicing, splicing changes, study, syndrome, tissue, total energy intake, transcriptome

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