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Food insecurity promotes adiposity in mice

ABSTRACT: The obesity epidemic continues to challenge global health, driven by multifaceted environmental and biological factors. Here, we investigate the impact of food insecurity, characterized by unpredictable food access, on body weight, food intake, and body composition in mice. Male and female C57BL/6J mice were subjected to a combination of intermittent fasting and 5% calorie restriction to resemble food insecurity situations. Our results reveal that this novel food insecurity model promotes fat accumulation and decreases lean mass in both sexes on a standard chow diet. While food insecurity did not exacerbate fat gain in male mice fed a high-fat diet, it further reduced lean mass. RNA sequencing of epididymal white adipose tissue from food-insecure male mice identified upregulated lipid metabolism genes and downregulated immune response genes, suggesting adipocyte expansion and potential immunity dysfunction. These results challenge the traditional view that obesity is solely driven by positive energy balance. Instead, our findings highlight the role of food insecurity in promoting metabolic adaptations favouring fat storage. Our data provide biological mechanisms that may explain the dramatic rise in obesity, underscoring the importance of socio-economic factors, beyond diet composition and energy balance, in understanding the complex etiology of obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE274149 | GEO | 2025/06/04

REPOSITORIES: GEO

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Project description:Dietary protein restriction has been shown to increase energy expenditure and to improve insulin sensitivity in mice, but it is unknown whether humans exhibit similar phenotype to a prolonged eucaloric protein-restricted diet that meet daily protein minimum requirements. We hypothesize that a protein-restricted diet would necessitate an increase in energy intake in order to maintain body weight in healthy, lean men. We designed an overall amino acid diluted diet meeting the requirement for daily protein intake and essential amino acids. Healthy, young, lean men adhered to a protein-restricted, high-carbohydrate diet (LPHC: protein 9E%, 70E% carbohydrate, and 21E% fat) or a protein-restricted, high-fat diet (LPHF: 9E% protein, 50E% fat, and 40E% carbohydrate) for 5 weeks, followed by another 5 weeks on a higher, standard protein diet (HPD: 18E% protein), reflecting their habitual diet. The diets were eucaloric, and energy provision was adjusted to maintain body weight throughout the interventions. In addition, wild type (WT), and FGF21 knockout mice were also fed LPHC, LPHF diets, or a standard higher diet (HPD) for a total of 10 weeks. Our results showed that prolonged eucaloric LPHC and LPHF diets necessitated a daily increase of 20-21% (2.5 MJ) in food intake to maintain body weight compared to pre-intervention in healthy, lean men. Additionally, fasting plasma FGF21 levels increased from 90±125 pg/ml and 78±34 pg/ml to 257±99 pg/ml and 160±52 pg/ml at the end of the LPHC and LPHF, respectively. Furthermore, proteomic analysis revealed adaptations in the respiratory chain in human adipose tissue after 5-week protein-restricted diets. This was found to be dependent on FGF21 in mice, indicating increased energy utilization through alternative UCP1-independent futile cycle pathways likely mediated by FGF21. Moreover, whole-body insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, was increased by 16% after the LPHC intervention while maintained after the LPHF intervention, despite the high fat intake. These findings suggest that a protein-restricted diet could serve as a promising approach to prevent weight gain and comorbidities associated with obesity.

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Food insecurity promotes adiposity in mice

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