Biology subjects

Illiano, J.

Publications and source records attributed to Illiano, J..

4 recordsLinked to original sources

bioRxiv2026

Dietary sugar type determines the response to protein restriction in females, but not males

Low protein (LP) diets improve metabolic health in rodents and humans. In rodents, LP diets are typically implemented by replacing protein with carbohydrates like sucrose or cornstarch, keeping diets isocaloric. However, humans can choose from many different types of carbohydrate, and how dietary carbohydrate quality - the precise composition of the dietary sugars - impacts the response to dietary protein remains largely unexplored. Here, mice were fed control (21% protein) or LP (7% protein) diets with four different carbohydrate sources: sucrose, a 1:1 glucose/fructose mixture, glucose, or fructose. While LP diets improved metabolic health across all groups in male mice, carbohydrate quality also significantly altered specific health outcomes, with fructose-fed mice having the lowest body weight and adiposity of all control diets. In female mice, responses to LP diets were influenced by carbohydrate quality, with certain sugars inducing a stronger metabolic response to LP diets than previously seen. Finally, in female APP/PS1 mice, a model of Alzheimer's disease, we find that although LP diets reduce A-beta; plaque burden irrespective of carbohydrate type, dietary sugar type does influence spatial memory. Together, these results demonstrate that while dietary protein is a critical determinant of metabolic and neurological health, carbohydrate quality influences these outcomes in a sex-specific manner.

physiology↗

bioRxiv2025

A low protein diet drives short- and long-term improvements in metabolic health in a mouse model of sleeve gastrectomy

Despite the largely beneficial impact of bariatric surgery on obesity and metabolic disease, continued post-surgical obesity and weight recurrence is common and may be impacted by diet. While guidelines recommend a high-protein diet based on the theory that this will preserve lean mass, emerging evidence suggests that both humans and mice are metabolically healthier on low protein diets. We assessed the effect of varying dietary protein levels on post-surgical weight loss and weight regain in a mouse model of one type of bariatric surgery, sleeve gastrectomy. We found that a low protein diet optimally drives post-surgical weight loss, boosting energy expenditure and improving blood glucose regulation. Using a multi-omics approach, we identified clusters of differentially expressed genes and metabolites that correlated with these phenotypes and found that diet heavily influences the livers molecular response to sleeve gastrectomy. These results suggest that current post-surgical high protein guidelines may limit both the short-and long-term benefits of surgery, and a low protein diet may improve patient outcomes.

physiology↗

bioRxiv2025

Tissue-specific effects of dietary protein on cellular senescence are mediated by branched-chain amino acids

Dietary protein is a key regulator of healthy aging in both mice and humans. In mice, reducing dietary levels of the branched-chain amino acids (BCAAs) recapitulates many of the benefits of a low protein diet; BCAA-restricted diets extend lifespan, reduce frailty, and improve metabolic health, while BCAA supplementation shortens lifespan, promotes obesity, and impairs glycemic control. Recently, high protein diets have been shown to promote cellular senescence, a hallmark of aging implicated in many age-related diseases, in the liver of mice. Here, we test the hypothesis that the effects of high protein diets on metabolic health and on cell senescence are mediated by BCAAs. We find that reducing dietary levels of BCAAs protects male and female mice from the negative metabolic consequences of both normal and high protein diets. Further, we identify tissue-specific effects of BCAAs on cellular senescence, with restriction of all three BCAAs - but not individual BCAAs - protecting from hepatic cellular senescence while potentiating cell senescence in white adipose tissue. We find that the effects of BCAAs on hepatic cellular senescence are cell-autonomous, with lower levels of BCAAs protecting cultured cells from antimycin-A induced senescence. Our results demonstrate a direct effect of a specific dietary component on a hallmark of aging and suggest that cellular senescence may be highly susceptible to dietary interventions.

physiology↗

bioRxiv2024

Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer&aposs disease

Caloric restriction (CR) is a widely recognized geroprotective intervention that slows or prevents Alzheimers disease (AD) in animal models. CR is typically implemented via feeding mice a single meal per day; as CR mice rapidly consume their food, they are subject to a prolonged fast between meals. While CR has been shown to improve metabolic and cognitive functions and suppress pathological markers in AD mouse models, the specific contributions of fasting versus calorie reduction remains unclear. Here, we investigated the contribution of fasting and energy restriction to the beneficial effects of CR on AD progression. To test this, we placed 6-month-old 3xTg mice on one of several diet regimens, allowing us to dissect the effects of calories and fasting on metabolism, AD pathology, and cognition. We find that energy restriction alone, without fasting, was sufficient to improve glucose tolerance and reduce adiposity in both sexes, and to reduce A{beta} plaques and improve aspects of cognitive performance in females. However, we find that a prolonged fast between meals is necessary for many of the benefits of CR, including improved insulin sensitivity, reduced phosphorylation of tau, decreased neuroinflammation, inhibition of mTORC1 signaling, and activation of autophagy, as well as for the full cognitive benefits of CR. Finally, we find that fasting is essential for the benefits of CR on survival in male 3xTg mice. Overall, our results demonstrate that fasting is required for the full benefits of a CR diet on the development and progression of AD in 3xTg mice, and suggest that both when and how much we eat influences the development and progress of AD.

physiology↗