open access publication

Preprint, 2023

Impact of dietary macronutrient composition on gene regulation in adipose tissue

In: Research Square, 10.21203/

Contributors (8)

Farris, Kathryn M (0000-0002-7599-8050) [1] Senior, Alistair Mcnair [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 J (0000-0003-2605-6435) Nobrega, Marcelo A (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 tissue, caloric intake, carbohydrates, changes, components, composition, content, diet, dietary composition, dietary fat content, dietary macronutrient composition, distinct mechanisms, distinct sets, energy, energy intake, environmental changes, expression, expression changes, factors, fat, fat content, framework, function, gene expression, gene regulation, gene regulation responses, gene sets, genes, health, impact, importance, influence, insights, intake, interaction, isocaloric diets, lifestyle components, macronutrient composition, macronutrient interactions, mechanism, metabolic functions, metabolic health, nutritional geometry framework, parameters, phenomenon, physiological phenomena, plasticity, proportion, proportion of energy, protein, regulation, regulation response, response, role, separate gene sets, set, splicing, splicing changes, study, syndrome, tissue, total energy intake, transcriptome