Wheat Flour Intake Promotes Weight Gain and Metabolic Changes in Mice

TL;DR

Mice eating wheat flour gain weight and show metabolic changes even without eating more calories.

Contribution

Wheat flour promotes weight gain and metabolic changes in mice by reducing energy expenditure and altering lipid and amino acid metabolism.

Findings

Mice preferred wheat-based foods and gained weight despite similar caloric intake.

Wheat flour reduced energy expenditure and increased fatty acid synthesis and adiposity.

Blood metabolites showed increased fatty acids and decreased essential amino acids.

Abstract

This study examined the metabolic effects of wheat flour intake on body weight regulation in mice. Male and female C57BL/6 mice were given free access to standard chow and wheat‐based foods, including bread and baked wheat flour, and food preference, energy expenditure, hepatic gene expression, and blood metabolite profiles were analyzed. Mice showed a strong preference for wheat‐based foods, leading to significant body weight gain despite comparable caloric intake. Wheat flour consumption was associated with reduced energy expenditure, increased adiposity, and elevated circulating insulin and leptin levels. Blood metabolomic analysis revealed increased fatty acid levels and reduced essential amino acids, suggesting enhanced lipogenesis and a potential imbalance in amino acid intake. Consistently, hepatic expression of genes involved in fatty acid synthesis and lipid transport was upregulated. Importantly, withdrawal of wheat flour rapidly attenuated body weight gain and reversed the associated metabolic alterations. These findings demonstrate that wheat flour intake promotes obesity in mice primarily by decreasing energy expenditure and altering metabolic pathways independent of excess calorie consumption, highlighting wheat flour as a dietary factor that strongly influences energy homeostasis and body weight regulation.

When given a choice between standard chow and wheat‐based foods such as bread or baked wheat flour, mice consistently preferred the wheat products. This selective intake led to significant weight gain despite unchanged total caloric consumption. Wheat flour intake was associated with reduced energy expenditure, enhanced hepatic fatty acid synthesis, and altered blood metabolite profiles, including increased long‐chain fatty acids and decreased essential amino acids. These findings suggest that wheat flour, even without added sugars or fats, can disrupt energy balance and amino acid metabolism, contributing to obesity development.

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