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Diverging metabolic effects of two energy restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197285 | GEO | 2022/02/23

REPOSITORIES: GEO

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Project description:We investigated the regulation of adipose tissue (AT) gene expression during different phases of a dietary weight loss program and its relationship with insulin sensitivity. Obese women followed a weight reduction program composed of an energy restriction phase (ER) with a 4-week very-low-calorie diet and a weight stabilization period (WS) composed of a 2-month low-calorie diet followed by 3 to 4 months of a weight maintenance diet. At each time point, body composition, plasma parameters and glucose disposal rate were assessed and subcutaneous AT biopsies were performed. Variations in mRNA levels were determined using DNA microarrays and reverse transcription-quantitative PCR. Distinct sets of AT genes are regulated during calorie restriction and weight stabilization revealing an unexpected temporal pattern in the link between AT and insulin sensitivity during weight loss. Experiment Overall Design: Fifteen obese premenopausal women were recruited at the Third Faculty of Medicine of Charles University and at the Institute for Mother and Child Care in Prague, Czech Republic. During the first four weeks of the dietary intervention program, the subjects received an energy restricted diet of 800 kcal/day (liquid formula diet, Redita, Promil). During the next two months, a low-calorie diet was designed to provide 600 kcal/day less than the individually estimated energy requirement based on an initial resting metabolic rate multiplied by 1.3. Following this, subjects entered a weight maintenance phase for a period of 3 to 4 months, during which the patients were instructed to keep their weight stable. A complete clinical investigation in the fasting state was realized before and at the end of each phase. Needle microbiopsy of subcutaneous AT was performed under local anesthesia (1% Xylocaine) from the abdominal region (14â20 cm lateral to the umbilicus). Total RNA were isolated from AT samples with Qiagen RNeasy kit. RNA quantity and quality were checked with the Experion automated electrophoresis system (BioRad laboratories). We performed a whole transcriptome analysis comparing 1) before vs. after the initial 4 weeks severe energy restriction (ER), 2) after energy restriction vs. after weight stabilization (WS) and 3) before dietary intervention vs. after weight stabilization (DI). Eight subjects representative of the cohort were selected, matched for high quality of total RNA samples, insulin sensitivity and weight changes during the study. Targets for microarray experiments were generated from 500 ng of total RNA with Agilent low RNA input amplification kit (Agilent Technologies) and hybridized to whole genome 44k oligonucleotide arrays (Agilent Technologies). Each combination of samples was analyzed twice using a dye swap design (i.e., a total of 48 hybridizations). Data acquisition from microarrays was obtained with a GenePix 4000B scanner (Axon instruments) and image processing was performed with Feature Extraction 8.5 (Agilent Technologies). Raw data were normalized with a global Lowess procedure and filtered with R package LIMMA (Bioconductor). Outlier replicates and spots with a signal to noise ratio lesser than 2 on both red and green channel were eliminated from our analyses. Mean log ratios were calculated from paired duplicates before normalization. Differentially expressed genes were identified with Significance Analysis of Microarray (SAM) procedure.

Project description:Background: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown. Objective: We investigated the global AT gene expression profile before and after two different rates of weight loss that resulted in similar total weight loss, and after a subsequent weight stabilization period. Design: In this randomized controlled trial, 25 male and 28 female individuals (BMI: 28-35 kg/m2) followed either a low-calorie diet (LCD; 1250 kcal/d) for 12 weeks or a very-low-calorie diet (VLCD; 500 kcal/d) for 5 weeks (weight loss (WL) period) and a subsequent weight stable (WS) period of four weeks. The WL period and WS period together is termed dietary intervention (DI) period. Abdominal subcutaneous AT biopsies were collected for microarray analysis, and gene expression changes were calculated for all three periods in the LCD group, VLCD group and between diets (ΔVLCD-ΔLCD). Results: Weight loss was similar between groups during the WL period (LCD: -8.1±0.5 kg, VLCD: -8.9±0.4 kg, difference p=0.25). Overall, more genes were significantly regulated and changes in gene expression were more extreme in the VLCD group compared to the LCD group. Gene sets related to mitochondrial function, adipogenesis and immunity/inflammation were more strongly upregulated on a VLCD compared to a LCD during the DI period (positive ΔVLCD-ΔLCD). Neuronal- and olfactory-related gene sets were decreased during the WL period and DI period in the VLCD group. Conclusions: The rate of weight loss (LCD vs. VLCD), with similar total weight loss, strongly regulates AT gene expression. Increased mitochondrial function and adipogenesis on a VLCD compared to a LCD reflect potential beneficial diet-induced changes in AT, while differential neuronal and olfactory regulation suggest functions of these genes beyond the current paradigm.

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Diverging metabolic effects of two energy restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity

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