Significant Reduction In Fat Mass Research Articles

The Release of Lipolytic Hormones during Various High-Intensity Interval and Moderate-Intensity Continuous Training Regimens and Their Effects on Fat Loss.

To investigate the release of lipolytic hormones during various high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), and their effects on fat loss. 39 young women categorized as obese (with a body fat percentage (BFP) ≥30%) were randomly allocated to one of the following groups: all-out sprint interval training (SIT, n =10); supramaximal HIIT (HIIT120, 120%V̇O2peak, n = 10); HIIT (HIIT90, 90%V̇O2peak, n = 10), or MICT, (60%V̇O2peak, n = 9) for a twelve-week observation period consisting of 3 to 4 exercise sessions per week. Serum epinephrine (EPI) and growth hormone (GH) were measured during the 1st, 20th, and 44th training sessions. Body weight (BW), body mass index (BMI), whole-body fat mass (FM) and BFP were assessed pre- and post-intervention. Following the 1st and 20th sessions, significant increases in EPI (p < 0.05) were observed post-exercise in HIIT120 and HIIT90, but not in SIT and MICT. In the 44th session, the increased EPI was found in SIT, HIIT120, and HIIT90, but not in MICT (p < 0.05). For the GH, a significant increase was observed post-exercise in all groups in the three sessions. The increased EPI and GH returned to baselines 3 hours post-exercise. After the 12-week intervention, significant reductions in FM and BFP were found in all groups, while reductions in BW and BMI were only found in the SIT and HIIT groups. Greater reductions in FM and BFP, in comparison to MICT, were observed in the SIT and HIIT groups (p < 0.05). 12-week SIT, HIIT120, and HIIT90, in comparison to MICT, were more efficacious in fat reduction in obese women, partly benefiting from the greater release of lipolytic hormones during training sessions.

Effectiveness of high intensity and sprint interval training on metabolic biomarkers, body composition, and physical fitness in adolescents: randomized controlled trial.

The aim of this study was to evaluate the effect of HIIT and SIT programmes on body composition, blood pressure, lipid profile, glucose, cardiorespiratory fitness, and strength of adolescents and to compare the effect between those different protocols. Sixty adolescents were recruited from a high school and were randomly placed into three groups. SIT and HIIT undertook a training for 8 weeks, twice a week, for 12 min per session, during their Physical Education lessons. SIT group performed 6 sets of 60 s of work (90-95%HRmax) / 60 s of rest (50-55%HRmax), and HIIT group performed 3 sets of 2 min of work (80-85%HRmax) / 2 min of rest (50-55%HRmax). After adjustment by sex, both experimental groups exhibited a significant reduction in fat mass (p < 0.01), and trunk fat mass (p < 0.01), as well as a significant increase in lean mass (p = 0.01; <0.01), hand-grip strength (p < 0.01) and standing long jump (p = 0.05-0.04, respectively). In addition, HIIT showed a significant (p < 0.05) improvement in blood pressure, diastolic blood pressure, heart rate and VO2max, and a tendency toward a significant reduction in low density lipoprotein. The implementation of a HIIT protocol within high school Physical Education sessions, maintained for 8 weeks, at a rate of 3 sets of 2 min of work (80-85% RHR)/2 min of rest (50-55% RHR) generated adaptations such as improved fitness condition, changes in body composition, and improvements in blood parameters and blood pressure. However, the group of adolescents who performed SIT, shorter but more intense sets, did not experience as many benefits.

Efficacy of Interval Training in Improving Body Composition and Adiposity in Apparently Healthy Adults: An Umbrella Review with Meta-Analysis.

Although the efficacy of interval training for improving body composition has been summarized in an increasing number of systematic reviews in recent years, discrepancies in review findings and conclusions have been observed. This study aims to synthesize the available evidence on the efficacy of interval training compared with moderate-intensity continuous training (MICT) and nonexercise control (CON) in reducing body adiposity in apparently healthy adults. An umbrella review with meta-analysis was performed. A systematic search was conducted in seven databases (MEDLINE, EMBASE, Cochrane Database, CINAHL, Scopus, SPORTDiscus, and Web of Science) up to October 2023. Systematic reviews with meta-analyses of randomized controlled trials (RCTs) comparing interval training and MICT/CON were included. Literature selection, data extraction, and methodological quality assessment (AMSTAR-2) were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model. Subgroup analyses were conducted based on the type of interval training [high-intensity interval training (HIIT) and sprint interval training (SIT)], intervention duration, body mass index, exercise modality, and volume of HIIT protocols. Sixteen systematic reviews, including 79 RCTs and 2474 unique participants, met the inclusion criteria. Most systematic reviews had a critically low (n = 6) or low (n = 6) AMSTAR-2 score. Interval training demonstrated significantly greater reductions in total body fat percent (BF%) compared with MICT [weighted mean difference (WMD) of - 0.77%; 95% confidence interval (CI) - 1.12 to - 0.32%] and CON (WMD of - 1.50%; 95% CI - 2.40 to - 0.58%). Significant reductions in fat mass, visceral adipose tissue, subcutaneous abdominal fat, and android abdominal fat were also observed following interval training compared to CON. Subgroup analyses indicated that both HIIT and SIT resulted in superior BF% loss than MICT. These benefits appeared to be more prominent in individuals with overweight/obesity and longer duration interventions (≥ 12weeks), as well as in protocols using cycling as a modality and low-volume HIIT (i.e., < 15min of high-intensity exercise per session). This novel umbrella review with large-scale meta-analysis provides an updated synthesis of evidence with implications for physical activity guideline recommendations. The findings support interval training as a viable exercise strategy for reducing adiposity in the general population.

Do anti-obesity medical treatments have a direct effect on adipose tissue?

During the past years, several drugs have been developed for the treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists (RA), GLP-1/GIP biagonists and the melanocortin 4 receptor (MC4R) agonist, setmelanotide. Some should be available in the future: GLP-1/glucagon biagonists, GLP-1/GIP/glucagon triagonists. These drugs act mainly by reducing food intake or fat absorption. However, many of them show specific effects on the adipose tissue. All these drugs show significant reduction of fat mass and, more particularly of visceral fat. If most of the drugs, except orlistat, have been shown to increase energy expenditure in rodents with enhanced thermogenesis, this has not yet been clearly demonstrated in humans. However, biagonists or triagonist stimulating glucagon seem to a have a more potent effect to increase thermogenesis in the adipose tissue and, thus, energy expenditure. Most of these drugs have been shown to increase the production of adiponectin and to reduce the production of pro-inflammatory cytokines by the adipose tissue. GLP-1RAs reduce the size of adipocytes and promote their differentiation. GLP-1RAS and GLP-1/GIP biagonists reduce, in the adipose tissue, the expression of several genes involved in lipogenesis. Further studies are still needed to clarify the precise roles, on the adipose tissue, of these drugs dedicated for the treatment of obesity.

The effect of LCn-3 PUFA supplementation on body weight, body composition, and muscle function during alternate-day fasting (ADF)

During weight loss the loss of body mass is associated not only with body fat reduction but also with a decrease in fat-free mass (FFM), related to the reduction in muscle mass and function(1). Supplementation with long-chain n-3 fatty acids (LCn-3 PUFA), in the absence of caloric restriction, results in a significant decrease in fat mass and an increase in FFM(2) along with improvements in muscle mass and strength(3). However, the impact of supplementation with LCn-3 PUFA during weight loss) remains unknown. Therefore, the aim of this study was to explore the effects of LCn-3 PUFA supplementation, in the form of Krill oil (KO), during alternate day fasting (ADF) on body weight, fat mass loss, FFM and muscle function changes in healthy overweight and obese adults.A total of 41 men and women (age: 39.35 ± 10.4 years, BMI: 31.05 ± 4.2 kg/m2) completed the study (NCT06001632), in which they were randomised into either a KO or Placebo (PL) groups. Both groups carried out 8-weeks of ADF combined with intake of 4 g/day of the corresponding supplements. ADF involved consuming no more than 500 calories on the 'fast day’ and consuming food ad libitum on each 'feed day’. Data on body weight and body composition (TBF-300, Tanita, Manchester, UK), handgrip strength (Handheld Hydraulic Dynamometer, Vernier Jamar; England, UK), and time to conduct 5 repetition of chair rising test were obtained pre-and post-intervention. Changes from baseline within groups were assessed using paired samples t-test. Mixed analysis of variance (Mixed-ANOVA) was used to measure 2-way interactions between time and group to identify the differences between groups. All statistical analysis were conducted using IBM Statistical Package for the Social Sciences SPSS 28.0.In both groups, body mass decreased significantly (KO:-4.7 ± 0.4kg, p&lt;0.001; PL:-4.5 ± 0.4kg, p&lt;0.001), along with a significant reduction in fat mass (KO:-2.4 ± 0.5kg p&lt;0.001; PL:-2.3 ± 0.5kg p&lt;0.001), and FFM (KO:-0.6 ± 0.2kg p&lt;0.001; PL:-0.7 ± 0.2kg, p&lt;0.001), with no differences between groups. In the PL group, there was a reduction in handgrip strength (-0.9 ± 0.7 kg, p&lt;0.001), while there was no change in KO group (-0.2 ± 0.5 kg, p=0.1), with a significant difference between groups (p&lt;0.001). In the KO group there was a significant reduction in time to conduct chair rising test (-1.8 ± 0.9s, p&lt;0.05), with no change in the PL group (-0.3 ± 1.3s, p=0.2), with a significant difference between groups (p&lt;0.001).Supplementation with LCn-3 PUFA (4 g/day) during 8 weeks of ADF, applied to individuals living with overweigh and obesity, does not facilitate body or fat mass loss and does not diminish the reduction in FFM. However, it attenuated the reduction in muscle function in healthy overweight and obese adults.

Impacts of Non- and Whole-fat Milk Supplementation on Metabolism-Associated Fatty Liver Disease (MAFLD) in C57BL/6 Mice

Background: Metabolism-associated fatty liver disease (MAFLD) is a widespread metabolic disease affecting 25% of the global adult population following Westernized lifestyles. Lifestyle modifications, specifically adherence to healthy dietary patterns, are pivotal in preventing and mitigating this disease. Consuming milk and dairy products is considered a cornerstone of a healthy dietary pattern, gathering significant attention due to compelling evidence from observational studies. These studies suggest that a higher intake of milk and certain dairy products is associated with a reduced risk of MAFLD. However, the relative health benefits of high- compared to lower-fat milk is a current topic of interest, with ongoing debates about their equivalency in promoting metabolic health. Aims &amp; Hypothesis: In a MAFLD mouse model, we aim to determine the dependence of milk’s fat content on hepatic steatosis and lipid metabolic pathways by comparing whole- (WFM) to non-fat (NFM) milk supplementation in high-fat diet-fed mice (HFD). We hypothesize that both WFM and NFM will significantly improve HFD-induced hepatic lipid accumulation but via differential molecular mechanisms. Methods: Two cohorts of n=24 and n=36 6-week-old male C57BL/6 mice were acclimatized for one week, then randomly assigned to a HFD (45 kcal% fat) or a low-fat diet (LFD; 10 kcal% fat) control group. The HFD mice were randomized to either a WFM or NFM treatment of 0.425 mL milk for 8 weeks. At the end of the study, mice underwent an insulin tolerance and pyruvate tolerance test and body composition was measured. The animals were then euthanized, tissues were collected, and hepatic lipid metabolism was compared using western blot, histology, hepatic lipid assays, gas chromatography, and qPCR. Statistics were then completed using GraphPad Prism software 7.0, utilizing T-test, one-way ANOVA, and Tukey’s post-hoc tests with a p-value ≤ 0.05 considered as statistically significant. Results: Body weight gain was significantly reduced in NFM groups compared to HFD and WFM, accounted for by a significant reduction in fat mass. ITT was unaltered when corrected to baseline, but NFM groups had significantly higher PTT values when corrected to baseline. Overnight-fasted blood glucose was significantly reduced in NFM animals compared to WFM animals, suggesting an altered metabolic state between the two treatment groups. Histological results indicate a significant reduction in lipid accumulation by the NFM group compared to the HFD group (p&lt;0.05), with WFM trending towards a similar reduction (p=0.051). Hepatic triglyceride concentrations were significantly reduced in NFM animals compared to WFM and HFD animals, suggesting a greater effect of NFM in reducing hepatic steatosis. Hepatic molecular results display an enhancement of enzymes involved in fatty acid oxidation and export pathways in the NFM group. In contrast, WFM displays an enhancement of de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. Conclusion: The findings suggest that NFM may be more effective at reducing hepatic steatosis through enhanced fatty acid oxidation and export. WFM may reduce steatosis less effectively because of counteractive effects on fatty acid uptake and de novo lipogenesis versus beta-oxidation. These results provide mechanistic evidence of the protective effects of milk on MAFLD. The funding sources for this project include the Alberta Diabetes Institute Studentship Grant, CIHR Canadian Graduate Studentship, and Dairy Farmers of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract P146: Strength Training Effectiveness in Normal-Weight Type 2 Diabetes Amongst Asian Americans

Introduction: Normal weight type-2 diabetes (NWD), characterized by body mass index (BMI) below 25 kg/m 2 , is more prevalent amongst Asian Americans (AA). While recent studies have shown strength training (ST) was superior to aerobic (AER) or combination training (COMB) in lowering HbA1c levels in individuals with NWD, it is unclear if these exercises have the same effects across AA subgroups, which differentiate due to cultural norms. Methods: We used data from a 9-month randomized control trial for NWD (conducted in San Francisco Bay Area in 2019-2020) to evaluate the effectiveness of weekly planned ST, AER, and COMB training sessions for Chinese and Asian Indian populations. Our primary outcome was change in diabetic control (HbA1c). Secondary outcomes included changes in body composition (e.g. fat and lean mass) and muscle strength (e.g. leg extension).We performed intention-to-treat (ITT) and per-protocol analysis (PP, restricted to those with 50% minimum adherence) to evaluate changes to HbA1c and body composition using repeated measures ANOVA and paired t-tests. Results: Of 129 participants, 59 were Chinese (19 ST, 20 AER, 20 COMB), and 70 were Asian Indian (26 ST, 20 AER, 24 COMB). Average baseline HbA1c was 7.5% for both groups (p=0.96). Chinese participants (77.3%) showed higher adherence than Asian Indian (56.6%) participants. Chinese participants showed reduced HbA1c for each intervention group (ITT: ST -0.42% [-0.742, -0.11], AER -0.6% [-0.92 -0.28], and COMB -0.13% [-0.43, 0.17], all p &lt; 0.05), with AER intervention yielding the largest decrease (p&lt;0.01). Results from PP provided a similar conclusion. Asian Indians had no meaningful reductions in HbA1c levels ( ITT: ST -0.36% [-0.83, -0.11], AER 0.26% [-0.27, 0.78], and COMB -0.42% [-0.97, 0.13]. For body composition, Chinese participants showed significantly reduced FMI-Z (ST: -1.03 [-1.94, -0.12], AER: -0.17 [-0.31, -0.04], COMB: -0.17 [-0.23, -0.10]) in all intervention groups. Asian Indian participants only showed significant reduction in FMI-Z (fat mass adjusted for height, age, sex) in the ST group -0.22 [-0.40, -0.03]. Body composition changes were associated with improvement in HbA1c. Conclusion: Overall, AA persons in over 50% of prescribed exercise improved their diabetic control. In Chinese participants, all interventions lowered HbA1c with higher reductions observed in ST and AER interventions. They also experienced significant reductions in fat mass in all exercise interventions. Asian Indian participants showed no significant reductions in HbA1c in any exercise intervention, but showed significant reductions in fat mass in ST. By recognizing unique cultural and social factors that influence AA behaviors and choices, healthcare professionals can develop tailored interventions that foster cultural understanding, thus empowering individuals to take control of their health and reduce the burden of diabetes.

Effect of 1-Week Weight Loss While Maintaining Total Body Water on Jump Performance.

Jumping performance is influenced by body composition and excess fat mass impairs performance. Maintaining optimal fat mass and fat-free mass (FFM) is crucial for enhancing jump height. However, there is limited evidence on short-term weight loss programs that reduce fat mass without water restriction and their effects on muscle function and jumping performance. This study aimed to clarify the effects of a 1-week weight loss program on jumping height and muscle function of volleyball players. The weight loss group engaged in two 40 min slow-paced jogging sessions in addition to their daily training routine. Energy intake was restricted without limitations on water intake. Total body water and body composition using the deuterium dilution method, muscle strength, and jump height before and after 1 week were evaluated for those in the weight loss and control groups. Body mass was significantly reduced in the weight loss group (-2.7 ± 1.3%, p < 0.05) with a significant reduction in fat mass (-17.7 ± 10.7%, p < 0.05). Meanwhile, there were no significant changes in total body water or FFM. Muscle strength and power tests indicated no significant differences between the groups; no notable differences were observed in handgrip strength or knee extension torque. The height of a single vertical and continuous jump remained consistent pre- and postintervention in the control group. In the weight loss group, although the height of a single vertical jump exhibited a slight decline postintervention, the height of a continuous jump displayed no significant changes. The short-term weight loss program significantly reduced fat mass without compromising muscle function, which is crucial for sports performance. These findings may benefit other athletes who require fat mass reduction while maintaining muscle function and help create new programs during specific training phases.

Effect of combined administration of Acyl-CoA: Cholesterol acyltransferase 1 inhibitor and glucagon-like peptide 1 receptor agonist on a rodent model of diet-induced obesity

A glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide was approved for the treatment of obesity by the Food and Drug Administration. However, it can cause gastrointestinal events at high doses, limiting its broader use. Combining drugs with multiple mechanisms of action could enhance the weight-reducing effects while minimizing side effects. To this end, we investigated the combined effects of semaglutide and avasimibe, an acyl-CoA:cholesterol acyltransferase 1 (ACAT1) inhibitor, on weight reduction in diet-induced obesity mice. Two cohorts of mice were used: In cohort 1, mice were fed a high-fat (HF) diet for 12 weeks and then randomly assigned to the vehicle, avasimibe [10 mg/kg body weight (BW)], semaglutide (0.4 mg/kg BW), or combination groups. The drugs were administered via subcutaneous (sc) injections on a daily basis. In cohort 2, mice were fed an HF diet for 8 weeks and randomly assigned to the same four groups, but avasimibe was administered at a dose of 20 mg/kg BW, and the drugs were administered every 3 days. In cohort 1, semaglutide initially reduced food intake initially, but this effect was diminished with prolonged administration. Avasimibe, on the other hand, did not affect food intake but prevented weight gain to a lesser extent than semaglutide. Importantly, the combination treatment resulted in the greatest percentage of body weight reduction, along with lower plasma glucose and leptin levels compared to the semaglutide single-treatment group. Cohort 2 confirmed that the superior weight loss in the combination group compared to the other three groups was largely due to a significant reduction in fat mass. Histological analysis of inguinal adipose tissue showed smaller adipocyte size across all treatment groups compared to the vehicle group, with no significant differences among the treatment groups. Collectively, these findings suggest combining semaglutide and avasimibe could be an effective approach to weight management.

SAT649 Org43553, The First Low-molecular-weight Agonist Of The Human Luteinizing Hormone Receptor Induces Leanness And Energy Expenditure In Mice

Abstract Disclosure: D. Lizneva: None. A. Gumerova: None. K. Ievleva: None. O. Barak: None. F. Korkmaz: None. J. Gimenez Roig: None. T. Frolinger: None. G. Pevnev: None. F. Sultana: None. N. Kramskiy: None. S. Wizman: None. M. Orloff: None. A.R. Pallapati: None. S. Rojekar: None. V. Ryu: None. O. Moldavski: None. T. Yuen: None. M. Zaidi: None. We provide compelling evidence that LH is a pro–lean hormone, and that ORG43553, the first low-molecular-weight agonist of the luteinizing hormone receptor (LHCGR) induces leanness and promotes energy expenditure in mice. We detected Lhcgr transcripts in white adipose tissue (WAT) depots in male and female C57BL/6 mice (qPCR, IHC, RNAscope, Sanger sequencing), but not in Lhcgr-/- mice. Intraperitoneal AlexaFluor-488–labeled hCG bound to gonadal and subcutaneous fat pads in wild type mice, but not in Lhcgr-/- mice. Following i.v. 89Zr–LH injection, radioactivity was detected in mesenteric, inguinal and gonadal WAT. LH, hCG and ORG43553 rapidly induced ERK1/2 phosphorylation in differentiated 3T3.L1 cells. Female and male Lhcgr+/- mice on normal chow and high–fat diet, respectively, became obese, importantly, without changes in sex steroids. The gene–dosage effect of Lhcgr depletion suggests a dominant physiologic action of LH on body composition. 14–week–old male C57BL/6 mice were fed on high–fat diet and injected, i.p., with LH, hCG or vehicle, twice–a–week, for 6 weeks. Both LH and hCG markedly reduced body fat accrual (qNMR) but triggered a rise in serum testosterone. The hCG–induced lean phenotype persisted despite androgen receptor blockade by flutamide—confirming that the pro–lean actions of LH and hCG were largely independent of testosterone. Furthermore that LH failed to inhibit fat accrual in Lhcgr-/- mice testified to its action via the LHCGR. Injection of ORG43553 into male C57BL/6 mice for 9 weeks caused a significant reduction in fat mass (qNMR), with reduced WAT weight in fat depots. Remarkably, serum testosterone remained unchanged confirming that the anti–adiposity effect of ORG43553 was independent of testosterone. To study the mechanism of LHCGR activation on body fat, 3T3.L1 adipocytes were treated with hCG or ORG43553 for 12 hours. This resulted in reduced oil droplet accumulation. 3T3-L1–derived organoids treated with LH, hCG or ORG43553 also displayed a substantial reduction in the differentiated layer compared to vehicle–treated organoids. To study whether, in addition to reducing adipocyte differentiation, LHCGR agonism also enhanced thermogenesis, 3T3-L1 adipocytes were pretreated with ORG43553 for 1 hour before measuring oxygen consumption rate (OCR) on a Seahorse Xf96 Analyzer. ORG43553 increased OCR at baseline and upon oligomycin exposure, indicating mitochondria proton leak (thermogenesis). To confirm increased energy expenditure in vivo, mice were injected, s.c., with ORG43553 or vehicle. Oxygen consumption (VO2) and energy expenditure (EE) increased acutely in ORG43553–treated mice, with no change in locomotor activity. The findings suggest that ORG45335, which has been tested in humans for infertility, can potentially become a candidate drug for obesity. Presentation: Saturday, June 17, 2023

207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become standard-of-care for the pharmacological treatment of obesity by inducing clinically meaningful weight loss through a reduction in appetite. While these agents potently reduce fat mass, the caloric restriction also reduces skeletal muscle mass. Strategies to preserve skeletal muscle in the presence of caloric restriction are needed to improve weight loss quality in obese patents. Trevogrumab (∝-MSTN) and garetosmab (∝-ActA) are fully human monoclonal antibodies that potently inhibit two mediators of skeletal muscle atrophy: myostatin (MSTN) and activin A (ActA). We first tested the effects of ∝-MSTN, ∝-ActA and GLP-1RA (Semaglutide [Sema]) on body composition of diet-induced obese mice either alone or in combination. Sema (-29.8%) and ∝-MSTN/∝-ActA (-23.4%) produced significant reduction in fat mass after 4 weeks of treatment vs baseline. Adding MTSN and ActA blockade to Sema produced an additive effect on fat mass (-54.2%). This combination also increased lean mass by 9.8% vs a 1.9% loss with Sema alone. To test this in primates, we performed a 20-week study with the combined administration of either Sema + ∝-MSTN or Sema + ∝-MSTN and ∝-ActA in obese male cynomolgus monkeys. The combination of ∝-MSTN + Sema was sufficient to cause an additive effect on fat mass -43.9% vs -25.1% for Sema alone. The addition of ∝-ActA to the combination produced a similar reduction in fat (-49.6%). The Sema control group also lost -2.5% lean mass after 20 weeks; despite the significant reduction in fat mass, the addition of ∝-MSTN to Sema slightly increased lean mass over the same period (0.5%); the addition of ∝-ActA increased lean mass even further (6.2%). These data suggest the blockade of MSTN and ActA to GLP-1RA treatment could greatly improve the quality of weight loss with this class of anti-obesity agents. Disclosure J.Mastaitis: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. D.Gomez: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. V.Le rouzic: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Stec: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. N.Khan: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. E.Na: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. T.Mcwilliams: None. S.Min: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Sleeman: Employee; Regeneron Pharmaceuticals Inc. Funding Regeneron Pharmaceuticals Inc.

Long-term effects of GH therapy in adult patients with Prader-Willi syndrome: a longitudinal study.

Prader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS. In this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects. Waist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value= 0.0313 for all). Our results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity.

Central nervous system IL-17R expression influences weight gain by altering food-intake and fat-mass accumulation

Abstract Cytokines influence innate behaviors in mice and IL-17a may function within the hypothalamus to reduce food-intake. We examine contributions of nervous system IL-17R expression on mouse feeding behavior following obesogenic diet exposure. We crossed IL-17Ra f/fand Synapsin1-Cre or Na v1.8-Cre mice to generate pan-neuronal (Syn-Cre IL-17Ra f/f) or peripheral neuronal- (Na-v1.8-Cre IL17Ra f/f) IL-17R knockout mice, respectively. Body weights of male and female mice were measured over 10-weeks of 60% high-fat diet (HFD) feeding. 60% HFD fed male Syn-Cre IL-17Ra f/fand IL-17Ra f/fmice underwent metabolic phenotyping and body composition analyses. Syn-Cre IL-17Ra f/fand IL-17Ra f/fmice received CNS penetrant Nrf2 activator Dimethyl-Fumarate (DMF) to assess whether pharmacological inhibition of IL-17a secretion alters HFD induced weight gain. Male and female Syn-Cre IL-17Ra f/fbut not Na-v1.8-Cre IL17Ra f/fmice displayed a 15–20% reduction in bodyweight after 10-weeks of HFD feeding (male p=0.00046, female p=0.0061). DMF treatment did not impact body weight. Syn-Cre IL-17Ra f/ftrended towards a reduction in food-intake and meal numbers when compared to IL-17Ra f/fmice. Syn-Cre IL-17Ra f/fhad a significant reduction in fat mass (total p=0.01, %total p=0.04) and lean mass (total p=0.03 and %total p=0.04). In sum, loss of central but not peripheral nervous system expression of IL-17R robustly and significantly blunts weight gain following chronic exposure to an obesogenic diet. This decrease in body weight was associated with a decrease in total fat mass. Our data suggest that a population of IL-17R expressing neurons within the brain influence food-intake by modulating feeding behaviors associated with meal frequency. NIH funding sources include F31-DK127728 and T32-DK07563

The Effect of High-Intensity Interval Training Type on Body Fat Percentage, Fat and Fat-Free Mass: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared body compositional changes, including fat mass (FM), body fat percentage (BF%), and fat-free mass (FFM), between different types of high-intensity interval training (HIIT) (cycling vs. overground running vs. treadmill running) as well as to a control (i.e., no exercise) condition. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Thirty-six RCTs lasting between 3 to 15 weeks were included in the current systematic review and meta-analysis. RCTs that examined the effect of HIIT type on FM, BF%, and FFM were sourced from online databases including PubMed, Scopus, Web of Science, and Google Scholar up to 21 June 2022. HIIT (all modalities combined) induced a significant reduction in FM (weighted mean difference [WMD]: -1.86 kg, 95% CI: -2.55 to -1.18, p = 0.001) despite a medium between-study heterogeneity (I2 = 63.3, p = 0.001). Subgroup analyses revealed cycling and overground running reduced FM (WMD: -1.72 kg, 95% CI: -2.41 to -1.30, p = 0.001 and WMD: -4.25 kg, 95% CI: -5.90 to -2.61, p = 0.001, respectively); however, there was no change with treadmill running (WMD: -1.10 kg, 95% CI: -2.82 to 0.62, p = 0.210). There was a significant reduction in BF% with HIIT (all modalities combined) compared to control (WMD: -1.53%, 95% CI: -2.13, -0.92, p = 0.001). All forms of HIIT also decreased BF%; however, overground running induced the largest overall effect (WMD: -2.80%, 95% CI: -3.89 to -1.71, p = 0.001). All types of HIIT combined also induced an overall significant improvement in FFM (WMD: 0.51 kg, 95% CI: 0.06 to 0.95, p = 0.025); however, only cycling interventions resulted in a significant increase in FFM compared to other exercise modalities (WMD: 0.63 kg, 95% CI: 0.17 to 1.09, p = 0.007). Additional subgroup analyses suggest that training for more than 8 weeks, at least 3 sessions per week, with work intervals less than 60 s duration and separated by ≤90 s active recovery are more effective for eliciting favorable body composition changes. Results from this meta-analysis demonstrate favorable body composition outcomes following HIIT (all modalities combined) with overall reductions in BF% and FM and improved FFM observed. Overall, cycling-based HIIT may confer the greatest effects on body composition due to its ability to reduce BF% and FM while increasing FFM.

Usefulness of Ultrasound in Assessing the Impact of Bariatric Surgery on Body Composition: a Pilot Study

BackgroundBariatric surgery (BS) has a significant impact on body composition. The purpose of the study is to evaluate the usefulness of musculoskeletal ultrasound (MUS) to bioelectrical impedance (BIA) in the follow-up of patients undergoing BS in terms of body composition and quality of life (QoL).MethodsThis is a prospective pilot study including 32 subjects (75% female, mean age: 49.15 ± 1.9 years) who underwent BS. Fat mass (FM), lean mass (LM), and skeletal muscle index (SMI) were calculated by BIA. MUS measured subcutaneous fat (SF) and thigh muscle thickness (TMT) of the quadriceps. QoL was assessed by the Moorehead-Ardelt questionnaire. All these measurements were performed 1 month prior to BS and at 12-month follow-up.ResultsThe mean BMI decreased by 6.63 ± 1.25 kg/m2 (p=0.001). We observed significant reductions in FM (p=0.001) and SF (p=0.007) and in LM (p=0.001) but not in SMI and TMT. We found a correlation between the FM and SF (pre-surgical, r=0.42, p=0.01; post-surgical, r=0.52, p=0.003) and between SMI and TMT (pre-surgical, r=0.35, p=0.04; post-surgical, r=0.38, p=0.03). QoL test showed significant improvement (p=0.001). In addition, a correlation between the QoL questionnaire and TMT post-surgery (r=0.91, p=0.019) was observed. However, we did not find any statistically significant correlation between QoL assessment and SMI or LM.ConclusionsOur results suggest that MUS can be complementary to BIA for the evaluation and the follow-up of body composition after BS. TMT of quadriceps can provide relevant information about regional sarcopenia and has a significant correlation with QoL.Graphical

A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis

The ribosomal protein S6 kinase 1 (S6K1) is a relevant effector downstream of the mammalian target of rapamycin complex 1 (mTORC1), best known for its role in the control of lipid homeostasis. Consistent with this, mice lacking the S6k1 gene have a defect in their ability to induce the commitment of fat precursor cells to the adipogenic lineage, which contributes to a significant reduction of fat mass. Here, we assess the therapeutic blockage of S6K1 in diet-induced obese mice challenged with LY2584702 tosylate, a specific oral S6K1 inhibitor initially developed for the treatment of solid tumors. We show that diminished S6K1 activity hampers fat mass expansion and ameliorates dyslipidemia and hepatic steatosis, while modifying transcriptome-wide gene expression programs relevant for adipose and liver function. Accordingly, decreased mTORC1 signaling in fat (but increased in the liver) segregated with defective epithelial-mesenchymal transition and the impaired expression of Cd36 (coding for a fatty acid translocase) and Lgals1 (Galectin 1) in both tissues. All these factors combined align with reduced adipocyte size and improved lipidomic signatures in the liver, while hepatic steatosis and hypertriglyceridemia were improved in treatments lasting either 3 months or 6 weeks.

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits

BackgroundDietary changes impact human physiology and immune function and have potential as therapeutic strategies.ObjectiveAssess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define...

Оценка эффективности диетотерапии с модификацией белкового компонента у пациентов пожилого возраста с ожирением

Patients and methods. This study included 43 elderly patients with class I-III obesity, who were randomized into two groups: the study group (24 patients) and the comparison group (19 patients). Anthropometric and serum parameters were assessed in all patients before and after diet therapy: total protein, transaminases, triglycerides, cholesterol fractions, glucose, uric acid, potassium, calcium, magnesium, iron, vitamins A, B2, B6, B9, B12, E, C and 25(OH)D3. Patients in the study group received a modified version of the standard diet with calorie restriction up to 1700 kcal and with protein modification by including 36 g of a specialized product for 14 days. Patients in the comparison group received a variation of the standard diet with calorie restriction up to 1730 kcal. Results. In patients in the study group, there were positive dynamics of biochemical parameters (a significant decrease in the levels of total cholesterol, glucose, uric acid, an increase in serum concentrations of 25(OH) D3, vitamin E and B12, potassium, calcium, magnesium, and zinc) and body composition parameters (a significant reduction of fat mass, total fluid, a slight increase in muscle mass) against the background of diet therapy with the inclusion of a specialized food product. Conclusion. Thus, timely diagnosis and correction of eating disorders in the elderly is an important part of the prevention and rehabilitation of alimentary-dependent diseases. Key words: obesity, diet therapy, elderly

On- Versus Off-Bike Power Training in Professional Cyclists: A Randomized Controlled Trial.

To compare the effectiveness of resistance power training (RPT, training with the individualized load and repetitions that maximize power output) and cycling power training (CPT, short sprint training) in professional cyclists. The participants (20 [2]y, peak oxygen uptake 78.0 [4.4]mL·kg-1·min-1) were randomly assigned to perform CPT (n = 8) or RPT (n = 10) in addition to their usual training regime for 7 weeks (2sessions/wk). The training loads were continuously registered using the session rating of perceived exertion. The outcomes included endurance performance (8-min time trial and incremental test), as well as measures of muscle strength/power (1-repetition maximum and mean maximum propulsive power on the squat, hip thrust, and lunge exercises) and body composition (assessed by dual-energy X-ray absorptiometry). No between-group differences were found for training loads or for any outcome (P > .05). Both interventions resulted in increased time-trial performance, as well as in improvements in other endurance-related outcomes (ie,ventilatory threshold, respiratory compensation point; P < .05). A significant or quasi-significant increase (P = .068 and .047 for CPT and RPT, respectively) in bone mineral content was observed after both interventions. A significant reduction in fat mass (P = .017), along with a trend (P = .059) toward a reduced body mass, was observed after RPT, but not CPT (P = .076 for the group × time interaction effect). Significant benefits (P < .05) were also observed for most strength-related outcomes after RPT, but not CPT. CPT and RPT are both effective strategies for the improvement of endurance performance and bone health in professional cyclists, although the latter tends to result in greater improvements in body composition and muscle strength/power.

Metabolic and energetic benefits of microRNA-22 inhibition.

IntroductionWe previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as KDM3A, KDM6B, PPARA, PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.Research design and methodsWe now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several timepoints between week 12 and week 27 of age.ResultsWeekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue-specific manner.ConclusionsThese original findings suggest that microRNA-22-3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease.