Fructose-Induced Metabolic Dysfunction Is Dependent on the Baseline Diet, the Length of the Dietary Exposure, and Sex of the Mice.

High sugar intake, particularly fructose, is implicated in obesity and metabolic complications. On the other hand, fructose from fruits and vegetables has undisputed benefits for metabolic health. This raises a paradoxical question-how the same fructose molecule can be associated with detrimental health effects in some studies and beneficial in others.

The propensity of fructose to induce metabolic dysfunction is dependent on the baseline diet, length of the dietary exposure, and sex of the mice.

Background/objectives: Numerous studies have implicated high intake of sugar, particularly fructose, with the development of obesity and metabolic complications. On the other hand, fructose from fruits and vegetables has undisputed benefits for metabolic health. This paradox questions how the same fructose molecule can be associated with detrimental health effects in some studies and beneficial in others.

Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice.

The metabolic effects of sugars and fat lie at the heart of the "carbohydrate vs fat" debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n = 245) are maintained on one of 18 isocaloric diets for 18-19 weeks and their metabolic status is assessed through in vivo procedures and by in vitro assays involving harvested tissue samples.

Ketogenic Diet Combined with Moderate Aerobic Exercise Training Ameliorates White Adipose Tissue Mass, Serum Biomarkers, and Hepatic Lipid Metabolism in High-Fat Diet-Induced Obese Mice.

Obesity is a serious public health issue worldwide. Growing evidence demonstrates the efficacy of the ketogenic diet (KD) for weight loss, but there may be some adverse side effects such as dyslipidemia and hepatic steatosis. Aerobic exercise is a widely recognized approach for improving these metabolic markers.

Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles.

Secretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or changes in gut microbiota composition.

Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin.

Nutrient sensing pathways influence metabolic health and aging, offering the possibility that diet might be used therapeutically, alone or with drugs targeting these pathways. We used the Geometric Framework for Nutrition to study interactive and comparative effects of diet and drugs on the hepatic proteome in mice across 40 dietary treatments differing in macronutrient ratios, energy density, and drug treatment (metformin, rapamycin, resveratrol). There was a strong negative correlation between dietary energy and the spliceosome and a strong positive correlation between dietary protein and mitochondria, generating oxidative stress at high protein intake.

Macronutrient-induced modulation of periodontitis in rodents-a systematic review.

Context: Consumption of dietary macronutrients is associated with the progression of a wide range of inflammatory diseases, either by direct modulation of host immune response or via microbiome. This includes periodontitis, a disease affecting tooth-supporting tissues.

Objective: The aim of this work was to systematically review studies focusing on the effect of macronutrient (ie, carbohydrate, protein, fat) intake on periodontitis in rodents.

Dietary carbohydrate, particularly glucose, drives B cell lymphopoiesis and function.

While diet modulates immunity, its impact on B cell ontogeny remains unclear. Using mixture modeling, a large-scale isocaloric dietary cohort mouse study identified carbohydrate as a major driver of B cell development and function. Increasing dietary carbohydrate increased B cell proportions in spleen, mesenteric lymph node and Peyer's patches, and increased antigen-specific immunoglobulin G production after immunization.

Impact of dietary carbohydrate type and protein-carbohydrate interaction on metabolic health.

Reduced protein intake, through dilution with carbohydrate, extends lifespan and improves mid-life metabolic health in animal models. However, with transition to industrialised food systems, reduced dietary protein is associated with poor health outcomes in humans. Here we systematically interrogate the impact of carbohydrate quality in diets with varying carbohydrate and protein content.

Macronutrient Determinants of Obesity, Insulin Resistance and Metabolic Health.

Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases.

Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms-A Narrative Review.

The majority of the epidemiological evidence over the past few decades has linked high intake of fats, especially saturated fats, to increased risk of diabetes and cardiovascular disease. However, findings of some recent studies (e.g.

Cardio-metabolic consequences of dietary carbohydrates: reconciling contradictions using nutritional geometry.

Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.

Plasma levels of trimethylamine-N-oxide can be increased with 'healthy' and 'unhealthy' diets and do not correlate with the extent of atherosclerosis but with plaque instability.

Aims: The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis.

Methods And Results: Plasma TMAO increased in mice on 'unhealthy' high-choline diets and notably also on 'healthy' high-fibre diets. Interestingly, TMAO was found to be generated by direct oxidation in the gut in addition to oxidation by hepatic flavin-monooxygenases.

Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control.

Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan.

The Effects of Metformin on Age-Related Changes in the Liver Sinusoidal Endothelial Cell.

Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied.

Ingestion of resistant starch by mice markedly increases microbiome-derived metabolites.

Recent research has shown significant health benefits deriving from high-dietary fiber or microbiome-accessible carbohydrate consumption. Compared with native starch (NS), dietary resistant starch (RS) is a high microbiome-accessible carbohydrate that significantly alters the gut microbiome. The aim of this study was to determine the systemic metabolic effects of high microbiome-accessible carbohydrate.

Sucrose and starch intake contribute to reduced alveolar bone height in a rodent model of naturally occurring periodontitis.

While there is a burgeoning interest in the effects of nutrition on systemic inflammatory diseases, how dietary macronutrient balance impacts local chronic inflammatory diseases in the mouth has been largely overlooked. Here, we used the Geometric Framework for Nutrition to test how the amounts of dietary macronutrients and their interactions, as well as carbohydrate type (starch vs sucrose vs resistant starch) influenced periodontitis-associated alveolar bone height in mice. Increasing intake of carbohydrates reduced alveolar bone height, while dietary protein had no effect.

Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice.

Calorie restriction (CR) increases lifespan and improves brain health in mice. Ad libitum low-protein, high-carbohydrate (LPHC) diets also extend lifespan, but it is not known whether they are beneficial for brain health. We compared hippocampus biology and memory in mice subjected to 20% CR or provided ad libitum access to one of three LPHC diets or to a control diet.

Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice.

BCL-2 proteins are known to engage each other to determine the fate of a cell after a death stimulus. However, their evolutionary conservation and the many other reported binding partners suggest an additional function not directly linked to apoptosis regulation. To identify such a function, we studied mice lacking the BH3-only protein BIM.

Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework.

Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content.

p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks.