Project description:Analysis of gene expression profiles in liver of obese 11 men/women on 10 days severe calorie-restricted diet and 8 men/women on ad libitum diet. This dataset is part of the TransQST collection.
Project description:We have carried out whole-genome expression profiling of whole blood from obese subjects, defined as obese diet-sensitive and obese diet-resistant, and well matched lean individuals. The diet-sensitive or diet-resistant status refers to the different rates of weight loss observed in the two groups on a low-calorie diet regimen. Bioinformatic analysis revealed alterations in transcription in key pathways that are consistent with impaired capacity for fatty acid oxidation driven mitochondrial ATP synthesis in obese subjects who are resistant to weight loss.
Project description:Objective: To examine the response of a calorie-restricted Dietary Approaches to Stop Hypertension diet on indicators of cardiometabolic health in a cohort of sedentary obese older adults. Design: This was a controlled-feeding trial with a parallel design. Each participant consumed either 3 oz (85 g; n = 15) or 6 oz (170.1 g; n = 13) of lean fresh beef within a standardized calorie-restricted DASH-like diet for 12-weeks. Fasted blood samples were collected and used to measure conventional biomarkers of cardiovascular, metabolic and inflammatory health. Participants: Caucasian older (70.8 years), obese (BMI: 32 ± 6.9 kg/m2; WC: 101 ± 16.4 cm) females (n = 17) and males (n = 11) from the rural community of Brookings, South Dakota. Results: 28 participants completed the 12-week feeding trial, with no differences (p > 0.05) among the biomarkers of cardiometabolic health between the 3 and 6 oz beef intake groups. However, when the beef intake groups were combined, all biomarkers changed concentration in response to the intervention diet. Total cholesterol (p < 0.001), LDL-C (p = 0.004), HDL-C (p < 0.0001), insulin (p = 0.014), glucose (p = 0.008), HOMA-IR (p < 0.05), IL-12 (p < 0.001), and CRP (p = 0.006) all decreased in response to the study diet. IGF-1 (p < 0.001) and IL-8 (p = 0.005) increased in response to the intervention. Correlations among cardiometabolic biomarkers and body composition measures were observed. By study end, the decrease in insulin (R 2 = 0.22; P = 0.012) and HOMA-IR (R 2 = 0.22; P = 0.01) was positively correlated with the decrease in waist circumference. The increase in IGF-1 was significantly correlated with the decrease in waist circumference (R 2 = 0.21; p = 0.014). The increase in IGF-1 was significantly correlated with the increase in sit-to-stand (R 2 = 0.21; p = 0.016). The increase in IL-8 was significantly correlated with decreases in total cholesterol (R 2 = 0.24; P = 0.008), LDL-C (R 2 = 0.17; P = 0.031) and glucose (R 2 = 0.44; P = 0.0001). Conclusions: These findings suggest that a DASH-like diet with restricted calories may potentially improve biomarkers of cardiometabolic health in sedentary obese older adults. These results also point to interrelationships between body composition changes and changes in cardiometabolic biomarkers. Lastly, regardless of meat intake amount, positive impacts on cardiometabolic biomarkers were observed in this cohort of older adults with an obese phenotype.
Project description:We have carried out whole-genome expression profiling of whole blood from obese subjects, defined as obese diet-sensitive and obese diet-resistant, and well matched lean individuals. The diet-sensitive or diet-resistant status refers to the different rates of weight loss observed in the two groups on a low-calorie diet regimen. Bioinformatic analysis revealed alterations in transcription in key pathways that are consistent with impaired capacity for fatty acid oxidation driven mitochondrial ATP synthesis in obese subjects who are resistant to weight loss. A total of 80 samples are analyzed. This consists of 20 lean subjects studied at one timepoint and 20 obese subjects (10 diet-sensitive and 10 diet-resistant) studied at 3 timepoints during caloric restriction (day of entry into program, week 3 into the program and week 6 into the program)
Project description:Semaglutide is an anti-diabetes and weight loss drug that decreases food intake, slows gastric emptying, and increases insulin secretion. Patients begin treatment with low-dose semaglutide and increase dosage over time as efficacy plateaus. With increasing dosage, there is also greater incidence of gastrointestinal side effects. One reason for the plateau in semaglutide efficacy despite continued low food intake is due to compensatory actions whereby the body becomes more metabolically efficient to defend against further weight loss. Mitochondrial uncoupler drugs decrease metabolic efficiency, therefore we sought to investigate the combination therapy of semaglutide with the mitochondrial uncoupler BAM15 in diet-induced obese mice. Mice were fed high-fat western diet (WD) and stratified into six treatment groups including WD control, BAM15, low-dose semaglutide without or with BAM15, and high-dose semaglutide without or with BAM15. Combining BAM15 with either semaglutide dose decreased body fat and liver triglycerides, which was not achieved by any monotherapy, while high-dose semaglutide with BAM15 had the greatest effect on glucose homeostasis. This study demonstrates a novel approach to improve weight loss without loss of lean mass and improve glucose control by simultaneously targeting energy intake and energy efficiency. Such a combination may decrease the need for semaglutide dose escalation and hence minimize potential gastrointestinal side effects.
Project description:This study examined the effect of the Dietary Approaches to Stop Hypertension (DASH) diet containing lean red meat on measures of body composition and muscle strength in a cohort of obese adults 65 and older; 36 males (n = 15) and females (n = 21) consumed 1800 kcal/day for 12 weeks under controlled feeding conditions. The study diet included daily intakes of 126 g of meat. Measures of body composition and muscle strength were obtained at weeks 0, 3, 6, 9, and 12. Breakfast, lunch, and dinner were provided every day for 12 weeks, and equal portions of meat were distributed at each meal. Significant effects of the study diet were detected across time for total body weight, body mass index (BMI), waist circumference, hip circumference, body fat percentage, absolute fat mass (AFM), and blood pressure such that a decrease (p < 0.001) was observed over 12 weeks. Significant effects of the study diet were detected across time for sit/stand (p < 0.001) such that an increase was observed. From baseline to study end, total body weight decreased by 6.3% (p < 0.001), body fat percentage decreased by 2.5% (p < 0.001), and absolute fat mass (AFM) decreased by 4.4 kg (p < 0.001). By the study end, skeletal muscle mass (SMM) was positively correlated with handgrip strength (R2 = 0.75; p = 0.001) and resting energy expenditure (REE) (R2 = 0.29; p = 0.001). Handgrip strength, gait, balance, and resting energy expenditure (REE) were well maintained (p > 0.05) throughout the study. These findings suggest that the DASH diet has the potential to be a tool to preserve muscle strength while reducing fat mass in obese older adults.
Project description:The goal of the present study was to evaluate the sweet taste function in obese rats fed with a 30% calorie-restricted cafeteria diet (CAFR) and/or subjected to moderate treadmill exercise (12-17 m/min, 35 min, 5 days per week) for 9 weeks. A two-bottle preference test, a taste reactivity test, and a brief-access licking test were carried out when animals were aged 21 weeks; biometric and metabolic parameters were also measured along the interventions. Two separate experiments for females and males were performed. Behaviorally, CAF diet decreased sucrose intake and preference, as well as perceived palatability, in both sexes and decreased hedonic responses in males. Compared to the CAF diet, CAFR exerted a corrective effect on sweet taste variables in females by increasing sucrose intake in the preference test and licking responses, while exercise decreased sucrose intake in both sexes and licking responses in females. As expected, CAF diet increased body weight and Lee index and worsened the metabolic profile in both sexes, whereas CAFR diet ameliorated these effects mainly in females. Exercise had no noticeable effects on these parameters. We conclude that CAF diet might diminish appetitive behavior toward sucrose in both sexes, and that this effect could be partially reverted by CAFR diet in females only, while exercise might exert protective effects against overconsumption of sucrose in both sexes.
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.
Project description:The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.
Project description:BackgroundObesity is a prevalent health problem in patients with schizophrenia, and calorie restriction diet (CRD) achieved effective weight loss and metabolic improvement; however, these have not been rigorously evaluated in obese patients with schizophrenia.ObjectiveTo measure the effects of CRD on weight loss and metabolic status in hospitalized obese women with schizophrenia during a 4-week period.MethodsParticipants were randomly assigned to two groups in a 1:1 ratio. The intervention group (n = 47) was asked to follow a CRD and the control group (n = 48) a normal diet for 4 weeks. Outcomes of body weight, body composition, as well as metabolic parameters were measured at baseline and following the intervention period.ResultsForty-five participants completed the 4-week research in both the intervention and control groups. Compared to the normal diet, adherence to the CRD significantly decreased body weight (2.38 ± 1.30 kg), body mass index (0.94 ± 0.52 kg/m2), waist circumference (4.34 ± 2.75 cm), hip circumference (3.37 ± 2.36 cm), mid-upper circumferences, triceps skin-fold thickness, fat mass and free fat mass with large effect sizes (p = <0.001, ηp2 range between 0.145 and 0.571), as well as total cholesterol (0.69 ± 0.70 mmol/L) with a medium effect size (p = 0.028, ηp2 = 0.054). There were no differences between the CRD and control groups in terms of pre-post changes in triglycerides, high- and low-density lipoprotein-cholesterols, as well as systolic and diastolic blood pressures (p > 0.05).ConclusionCRD is preventative of weight gain, but not apparent in intervention for metabolic status in hospitalized obese women with schizophrenia.Clinical trial registration: http://www.chictr.org.cn, ChiCTR-INR-16009185.