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Diet Composition Shapes Sleep, Quality of Life, and Gene Expression in Obesity: A Randomized Trial.

ABSTRACT: Obesity affects quality of life and sleep, making effective weight loss an attractive intervention. The role of diet composition on outcomes has not been determined. Our aim is to compare a ketogenic diet against an isocaloric balanced diet for effects on quality of life, sleep, circadian rhythm and gene expression in obesity. Twenty-four people affected by obesity completed the study. Volunteers were randomized to a 1200 Kcal ketogenic diet or balanced diet for 30 days, and all were encouraged to walk 30 minutes every day. Questionnaires for assessing quality of life and sleep were administered at baseline and at the end of the study. In a subgroup of 20 people actigraphy was performed to objectively capture sleep parameters, and circulating whole blood gene expression analysis was undertaken. Quality of life assessed with the IWQOL-Lite significantly improved after both diets (p<0.001), with the ketogenic diet showing a greater effect (p=0.006). The ketogenic diet also resulted in greater improvement in subjective sleep quality (p=0.023). Both diets improved daytime sleepiness (balanced diet p=0.012; ketogenic diet p=0.021). The ketogenic diet induced a greater weight loss (p=0.026). Gene expression analysis revealed greater changes in lipid metabolism with ketogenic diet. No significant changes in circadian genes were seen. Weight loss with diet intervention significantly improved quality of life of people with obesity, already after 30 days. The ketogenic diet resulted in greater improvements, in parallel with greater weight loss. Both diets influenced the expression of many metabolic genes in whole blood, with greater changes in lipid metabolism seen with ketogenic diet. Weight loss with diet intervention is effective to improve quality of life, sleep, and daytime sleepiness symptoms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE323980 | GEO | 2026/03/10

REPOSITORIES: GEO

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Project description:Objective Obesity is a multidimensional condition that is treatable by the restoration of a lean phenotype; however, some obesity-related outcomes may persist after weight normalization. Among the organs of the human body, the brain possesses a relatively low regenerative capacity and could retain perturbations established as a result of developmental obesity. Calorie restriction (CR) or a restricted ketogenic diet (KD) are successfully used as weight loss approaches, but their impact on obesity-related effects in the brain have not been previously evaluated. Methods We performed a series of experiments in a rat model of developmental obesity induced by a 12-week cafeteria diet, followed by CR to implement weight loss. First, we assessed the impact of obesity on neurogenesis (BrdU incorporation into the hippocampus), cognitive function (water maze), and concomitant changes in hippocampal protein expression (GC/MS-MS, western blot). Next, we repeated these experiments in a rat model of weight loss induced by CR. We also measured mitochondrial enzyme activity in rats after weight loss during the fed or fasting state. By using a modified version of the water maze we evaluated cognitive abilities in rats subjected to weight loss by CR or a restricted KD. Results In this study, obesity affected metabolic processes, upregulated hippocampal NF-κB, and induced proteomic differences which were associated with impaired cognition and neurogenesis. Weight loss improved neurogenesis and enhanced cognition. While the expression pattern of some proteins persisted after weight loss, most of the changes appeared de novo revealing metabolic adjustment by overactivation of citrate synthase and downregulation of ATP synthase. As a consequence of fasting, the activity of these enzymes indicated hippocampal adaptation to negative energy balance during the weight loss phase of CR. Moreover, the effects on cognitive abilities measured after weight loss were negatively correlated with the obesity level and were alleviated by KD, which improved cognition when used as a weight loss approach. Conclusions The study shows that cognition and mitochondrial metabolism in the hippocampus are affected by CR- or KD-induced weight loss.

Project description:Background: Despite the established relation between energy restriction and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still subject of debate. Objectives: The aim of the study was to examine the additional effects of nutrient quality on top of energy restriction(ER). Methods: A parallel-designed 12-week 25%ER dietary intervention study was conducted. Participants aged 40-70 years with abdominal obesity were randomized over three groups: a 25%ER high nutrient quality diet (n = 40); a 25%ER low nutrient quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, the high nutrient quality ER diet was enriched in monounsaturated and n-3 polyunsaturated fatty acids, fiber, and plant protein and reduced in fructose. Before and after the intervention intra-hepatic lipids, body fat distribution, fasting and postprandial responses to a mixed meal shake challenge test of cardio-metabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. Results: The high quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an anti-atherogenic lipoprotein profile and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low quality ER diet. Explorative analyses showed that the difference in weight loss between both ER diets were specifically present in insulin sensitive subjects (HOMA-IR ≤ 2.5), in whom the high nutrient quality diet induced 3.9 kg more weight loss than the low nutrient quality diet. Conclusion: A high nutrient quality 25%ER diet is more beneficial for cardiometabolic health than a low nutrient quality 25%ER diet. Overweight insulin sensitive subjects may benefit more from a high than a low nutrient quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue. Trial registration: ClinicalTrials.gov NCT02194504.

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Diet Composition Shapes Sleep, Quality of Life, and Gene Expression in Obesity: A Randomized Trial.

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