Reduction In Lean Body Mass Research Articles

Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis.

Diabetes is an independent risk factor for muscle mass loss, with possible mechanisms including impaired insulin signalling and chronic inflammation. The use of a glucagon-like peptide 1 (GLP-1) receptor-based agonist could lead to weight reduction, which might result from the loss of both fat and skeletal muscle. However, the body composition-modifying effects of GLP-1 receptor-based agonists have not been systematically characterized. PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to October 2023. Randomized controlled trials of GLP-1 receptor agonist or glucose-dependent insulinotropic polypeptide/GLP-1 receptor dual agonist, which reported the changes of body composition, were included. The results were computed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) in a random-effects model. In all, 19 randomized controlled trials were included. When compared with controls, substantial reductions in fat body mass were observed in patients using GLP-1 receptor-based agonist treatment (WMD = -2.25 kg, 95% CI -3.40 to -1.10 kg), with decrease in areas of both subcutaneous fat (WMD = -38.35 cm2, 95% CI, -54.75 to -21.95 cm2) and visceral fat (WMD = -14.61 cm2, 95% CI, -23.77 to -5.44 cm2). Moreover, greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users compared with non-users (WMD = -1.02 kg, 95% CI, -1.46 to -0.57 kg), while the changes in lean mass percentage were comparable between GLP-1 receptor-based agonist users and non-users. Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in lean mass percentage were comparable between the users and non-users.

Effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass on body composition.

There is limited data with respect to body composition changes for laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB). The objective of this study was to analyse changes in body composition between these two procedures during the first year after bariatric surgery. A prospective study was performed in patients undergoing bariatric surgery at two tertiary hospitals between 2017 and 2023. Body composition was assessed with dual-energy x-ray absorptiometry immediately before surgery, and at 1-, 6-, 12-, 18- and 24-months post-operatively, with a subgroup analysis performed for patients who undertook a scan at 18- and 24-months. Total weight loss (TWL), body mass index (BMI), fat mass (FM), lean body mass (LBM) and bone mineral content (BMC) parameters were compared between SG and RYGB. Forty-five patients were included in this series (SG n = 30, RYGB n = 15). There was a significant reduction in mean %TWL of 26.94 ± 8.86% and mean BMI of 11.12 ± 3.70 kg/m2 over 12-months. LBM accounted for 17.8% of TWL over 12-months, SG and RYGB did not differ in terms of loss of FM or LBM. For both procedures, the loss of LBM appeared to plateau at 6-months post-operatively. The only statistically significant finding between the two procedures was that RYGB resulted in an additional 0.06 kg loss compared with SG. SG and RYGB have been shown to have comparable weight loss and body composition changes in the short-to-medium term following surgery. LBM reduction was most significant in the early post-operative period across the entire cohort.

Changes in body composition in early breast cancer patients treated with aromatase inhibitors

PurposeThe aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).MethodsThis is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors.ResultsA significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean −3.1%, 95% CI −3.9; −2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from−1.3% to −3.9%, respectively.ConclusionAromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.

Chronic kidney disease (CKD) is associated with significant reductions in lean body mass and in the mass of various tissues, including skeletal muscle, which causes fatigue and contributes to high mortality rates. In CKD, the cellular protein turnover is imbalanced, with protein degradation outweighing protein synthesis, leading to a loss of protein and cell mass, which impairs tissue function. As CKD itself, skeletal muscle wasting, or sarcopenia, can have various origins and causes, and both CKD and sarcopenia share common risk factors, such as diabetes, obesity, and age. While these pathologies together with reduced physical performance and malnutrition contribute to muscle loss, they cannot explain all features of CKD-associated sarcopenia. Metabolic acidosis, systemic inflammation, insulin resistance and the accumulation of uremic toxins have been identified as additional factors that occur in CKD and that can contribute to sarcopenia. Here, we discuss the elevation of systemic phosphate levels, also called hyperphosphatemia, and the imbalance in the endocrine regulators of phosphate metabolism as another CKD-associated pathology that can directly and indirectly harm skeletal muscle tissue. To identify causes, affected cell types, and the mechanisms of sarcopenia and thereby novel targets for therapeutic interventions, it is important to first characterize the precise pathologic changes on molecular, cellular, and histologic levels, and to do so in CKD patients as well as in animal models of CKD, which we describe here in detail. We also discuss the currently known pathomechanisms and therapeutic approaches of CKD-associated sarcopenia, as well as the effects of hyperphosphatemia and the novel drug targets it could provide to protect skeletal muscle in CKD.

Metabolic dysfunction and the development of physical frailty: an aging war of attrition.

The World Health Organization recently declared 2021-2030 the decade of healthy aging. Such emphasis on healthy aging requires an understanding of the biologic challenges aging populations face. Physical frailty is a syndrome of vulnerability that puts a subset of older adults at high risk for adverse health outcomes including functional and cognitive decline, falls, hospitalization, and mortality. The physiology driving physical frailty is complex with age-related biological changes, dysregulated stress response systems, chronic inflammatory pathway activation, and altered energy metabolism all likely contributing. Indeed, a series of recent studies suggests circulating metabolomic distinctions can be made between frail and non-frail older adults. For example, marked restrictions on glycolytic and mitochondrial energy production have been independently observed in frail older adults and collectively appear to yield a reliance on the highly fatigable ATP-phosphocreatine (PCr) energy system. Further, there is evidence that age-associated impairments in the primary ATP generating systems (glycolysis, TCA cycle, electron transport) yield cumulative deficits and fail to adequately support the ATP-PCr system. This in turn may acutely contribute to several major components of the physical frailty phenotype including muscular fatigue, weakness, slow walking speed and, over time, result in low physical activity and accelerate reductions in lean body mass. This review describes specific age-associated metabolic declines and how they can collectively lead to metabolic inflexibility, ATP-PCr reliance, and the development of physical frailty. Further investigation remains necessary to understand the etiology of age-associated metabolic deficits and develop targeted preventive strategies that maintain robust metabolic health in older adults.

Effectiveness of an intermittent fasting diet versus regular diet on fat loss in overweight and obese middle-aged and elderly people without metabolic disease: a systematic review and meta-analysis of randomized controlled trials

ObjectiveAs the number of adults aged over 40 with obesity increases dramatically, intermittent fasting interventions (IF) may help them to lose fat and weight. This systematic review investigated the most recent research on the effects of intermittent fasting and a regular diet on body composition and lipids in adults aged over 40 with obesity without the metabolic disease. Data sourcesRandomized controlled trials (RCTs) on IF on adults aged over 40 with obesity were retrieved from PubMed, Web of Science, EBSCO, China Knowledge Network (CNKI), VIP database, Wanfang database with the experimental group using IF and the control group using a regular diet. Revman was used for meta-analysis. Effect sizes are expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). Study selectionA total of 9 articles of randomised controlled trials that met the requirements were screened for inclusion. Studies typically lasted 2–6 weeks. The experimental population was aged 42–66 years, with a BMI range of 25.7−35 kg/m2. SynthesisA total of 9 RCTs were included. meta-analysis showed that body weight (MD: −2.05 kg; 95% CI (−3.84, −0.27); p = 0.02), BMI (MD: −0.73 kg/m2; 95% CI (−1.05, −0.41); p < 0.001), fat mass (MD: −2.14 kg; 95% CI (−3.81, 0.47); p = 0.01), and TG (MD = −0.32 mmol/L, 95% CI (−0.50, −0.15, p < 0.001) were significantly lower in the experimental group than in the control group. No significant reduction in lean body mass (MD: −0.31 kg; 95% CI (−0.96, 0.34); p = 0.35). ConclusionIF had a reduction in body weight, BMI, fat mass, and TG in adults aged over 40 with obesity without metabolic disease compared to RD, and IF did not cause a significant decrease in lean body mass, which suggests healthy and effective fat loss. However, more long-term and high-quality trials are needed to reach definitive conclusions.

Relationship between sodium-glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

This study aims to assess the association between sodium-glucose cotransporter type-2 inhibitor (SGLT-2i) treatment and muscle atrophy in patients with type 2 diabetes mellitus (T2DM). We searched six databases from 1 January 2012 to 1 May 2023, without language restrictions. The primary outcome was muscle. Secondary outcomes were weight loss, weakness, malaise, or fatigue. Subgroup analyses were performed according to different definitions of muscle, treatment duration, and measurement methods. The quality of the studies was assessed using the Cochrane tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Nineteen randomized controlled trials (RCTs) involving 1,482 participants were included. Compared with the control group, a meta-analysis showed that T2DM participants in the group treated with SGLT-2i demonstrated statistically significant reductions in lean body mass of 0.66 (95% confidence interval (CI), -1.05 to -0.27; p = 0.0009) and skeletal muscle mass of 0.35 (95% CI, -0.66 to -0.04; p = 0.03). No deaths or serious adverse events were reported. The quality of evidence in the included trials was low. SGLT-2i may lead to a reduction in muscle strength in the treatment of T2DM compared to the control group. However, there is still a lack of high-quality evidence to evaluate muscle atrophy caused by SGLT-2i. https://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.

Early administration of postoperative BCAA-enriched PPN may improve lean body mass loss in gastric cancer patients undergoing gastrectomy

BackgroundIt has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss.MethodsWe conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery.ResultsAt postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (− 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups.ConclusionOur RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.

Metabolic disturbances in menopause

Menopause maybe associated with several short, medium and long-term consequences. Metabolic disturbances represent a significant negative effect of the progressive reduction of estradiol as well as of the increased androgens/estrogens ratio occurring during perimenopause (1). Besides, other hormonal (such as, hypercortisolism and/or altered thyroid function) or non-hormonal (family hystory, dietary habits, smoking, alcohol consumption, etc.) factors, could negatively impact on metabolism in an individualized manner. On the other hand, the ageing per se usually favours a change of body composition characterized by a reduction of lean body mass (LBM) and an increase of fat free mass (FFM), exposing post-menopausal women to higher cardiometabolic risk.

Correlation of Percentage Body Fat, Waist Circumference and Waist-to-Hip Ratio with Abdominal Muscle Strength.

Sedentary lifestyle and consumption of high-fat foods have become widespread, especially in the urban population. This leads to a reduction in lean body mass and increased body fat. The correlation between body fat indices and low back pain has been less explored and documented. The aim of this study was to identify the correlation between the percentage of body fat, waist circumference and waist-to-hip ratio and abdominal muscle strength. Percentage of body fat was estimated by using the body composition analyzer method using Tanita BC-545 Innerscan Segmental Body Composition. Waist-to-hip ratio was calculated by dividing the waist circumference by hip circumference. Abdominal muscle (rectus abdominis and external oblique) strength was measured by maximum voluntary isometric contraction as measured by surface electromyography. A positive correlation was observed between waist circumference and the percentage of body fat, while a negative correlation was observed between the average maximum voluntary isometric contraction of rectus abdominis and external oblique muscles and the percentage of body fat. Individuals with a high percentage of body fat tend to have higher fat distribution over the abdominal region and decreased abdominal muscle strength. Therapists should emphasize the use of abdominal muscles in individuals with high body fat in order to reduce the associated risk of the development of poor posture and low back pain.

Changes in Body Weight, Body Composition, Phase Angle, and Resting Metabolic Rate in Male Patients with Stage IV Non-Small-Cell Lung Cancer Undergoing Therapy.

Background and Objectives: Cancer treatments can adversely influence body weight status, body composition, phase angle (PhA), and resting metabolic rate (RMR), which could possibly affect disease course. Τhe aim was to assess differences in body composition, PhA, RMR, and related parameters in non-small-cell lung cancer (NSCLC) patients after treatment. Methods: The sample consisted of 82 NSCLC (stage IV) male patients (chemotherapy (C) 15.7%; immunotherapy (I) 13.3%; C + I 25.3%; (C) + radiotherapy (R) 22.9 %; and other 15.5%). Body weight and body composition, PhA, RMR, oxygen consumption (VO2), ventilation rate, and diet were assessed at baseline and at 3 months after initiation of therapy. Results: Reductions in PhA, RMR, VO2, ventilation rate, and intracellular water were observed at follow up. Weight loss was evident for 45% of patients who also had a reduction in lean body mass. In the group under C, lean mass was reduced at follow up (55.3 ± 11.53 vs. 52.4 ± 12.6, p = 0.04) without significant weight changes. In subjects with a low adherence to the Mediterranean diet (MedDietScore &lt; 30), RMR (1940 ± 485 vs. 1730 ± 338 Kcal, p = 0.001), VO2 (277.1 ± 70.2 vs. 247 ± 49.1 mL/min, p = 0.001), and ventilation rate (10.1 ± 2.28 vs. 9. ± 2 2.2 L/min, p = 0.03) were significantly reduced. The changes in body weight were positively related to % of change in fat mass (rho = 0.322, p = 0.003) and absolute lean mass change (rho = 0.534, p &lt; 0.001) and negatively associated with % of change in total body water (rho = -0.314, p = 0.004) (Spearman correlation coefficients). Conclusions: In conclusion, cancer therapy related to reductions in PhA and RMR, while lean mass reduction may be related to the type of treatment. Our results emphasize the importance of a more holistic nutritional and body composition assessment beyond body weight, to better address patients' needs in clinical practice.

Deletion of Jazf1 gene causes early growth retardation and insulin resistance in mice

Single-nucleotide polymorphisms in the human juxtaposed with another zinc finger protein 1 (JAZF1) gene have repeatedly been associated with both type 2 diabetes (T2D) and height in multiple genome-wide association studies (GWAS); however, the mechanism by which JAZF1 causes these traits is not yet known. To investigate the possible functional role of JAZF1 in growth and glucose metabolism in vivo, we generated Jazf1 knockout (KO) mice and examined body composition and insulin sensitivity both in young and adult mice by using 1H-nuclear magnetic resonance and hyperinsulinemic-euglycemic clamp techniques. Plasma concentrations of insulin-like growth factor 1 (IGF-1) were reduced in both young and adult Jazf1 KO mice, and young Jazf1 KO mice were shorter in stature than age-matched wild-type mice. Young Jazf1 KO mice manifested reduced fat mass, whereas adult Jazf1 KO mice manifested increased fat mass and reductions in lean body mass associated with increased plasma growth hormone (GH) concentrations. Adult Jazf1 KO manifested muscle insulin resistance that was further exacerbated by high-fat diet feeding. Gene set enrichment analysis in Jazf1 KO liver identified the hepatocyte hepatic nuclear factor 4 alpha (HNF4α), which was decreased in Jazf1 KO liver and in JAZF1 knockdown cells. Moreover, GH-inducedIGF-1 expression was inhibited by JAZF1 knockdown in human hepatocytes. Taken together these results demonstrate that reduction of JAZF1 leads to early growth retardation and late onset insulin resistance in vivo which may be mediated through alterations in the GH-IGF-1 axis and HNF4α.

Rapid Reduction In Lean Body Mass In Head And Neck Cancer Patients During Chemo- And Chemoradiotherapy

Rapid Reduction In Lean Body Mass In Head And Neck Cancer Patients During Chemo- And Chemoradiotherapy

Differences in body composition and growth persist postnatally in fetuses diagnosed with severe compared to mild fetal growth restriction.

Fetal growth restriction (FGR) is most commonly diagnosed in pregnancy if the estimated fetal weight (EFW) is < 10th%. Those with abnormal Doppler velocimetry, indicating placental insufficiency and pathological FGR, demonstrate reduced fat and lean mass compared to both normally growing fetuses and FGR fetuses with normal Dopplers. The aim of this study was to determine how severity of FGR and abnormal Doppler velocimetry impacts neonatal body composition. Among a cohort of fetuses with an EFW < 10th%, we hypothesized that those with abnormal Dopplers and/or EFW < 3rd% would have persistent reductions in lean body mass and fat mass extending into the neonatal period compared to fetuses not meeting those criteria. A prospective cohort of FGR fetuses with an estimated fetal weight (EFW) < 10th% was categorized as severe (EFW < 3rd% and/or abnormal Dopplers; FGR-S) versus mild (EFW 3-10th%; FGR-M). Air Displacement Plethysmography and anthropometrics were performed at birth and/or within the first 6-8 weeks of life. FGR-S versus FGR-M were born one week earlier (P = 0.0024), were shorter (P = 0.0033), lighter (P = 0.0001) with smaller weight-for-age Z-scores (P = 0.0004), had smaller head circumference (P = 0.0004) and lower fat mass (P = 0.01) at birth. At approximately 6-8 weeks postmenstrual age, weight, head circumference, and fat mass were similar but FGR-S neonates were shorter (P = 0.0049) with lower lean mass (P = 0.0258). Doppler velocimetry abnormalities in fetuses with an EFW < 10th% identified neonates who were smaller at birth and demonstrated catch-up growth by 6-8 weeks of life that favored fat mass accretion over lean mass and linear growth.

The importance of aerobic capacity and nutrition in recreational master mountain runners’ performance and race-induced changes in body composition and biochemical blood indices

This study aimed to explore the importance of aerobic capacity and nutrition on 28-km mountain running performance and race-induced changes in body composition and biochemical blood indices, in recreational master athletes of different performance levels. Twenty male master runners (age: 44.6 ± 7.7 years) were divided into two groups, slower and faster runners, according to their race performance. Maximum oxygen uptake [Formula: see text], velocity at [Formula: see text] [Formula: see text], oxygen consumption [Formula: see text], and velocity [Formula: see text] during the second ventilatory threshold were evaluated. Nutrition was assessed for one week before and during the race. Body composition was evaluated, and blood samples were collected before and 3 h after the race. Slower runners exhibited a greater reduction in lean body mass and greater changes in all muscle damage/inflammation/metabolism blood indices than the faster runners ( η2 = 0.201–0.927; p &lt; 0.05). When all the participants were assessed as one group ( n = 20), significant correlations were found between ([Formula: see text], vVO2Thr, race time, energy intake, expenditure, carbohydrate, protein intakes, and post-race changes in body composition and blood markers ( r: −0.825–0.824; p &lt; 0.05). The strongest determinants were ([Formula: see text] and vVO2Thr, while energy intake, expenditure, carbohydrate, and protein intakes seemed to be the weakest determinants of race performance and race-induced changes in body composition and blood indices. The results suggest that race-induced changes in body composition and blood indices are determined mainly by master runners’ race performance and endurance capacity and to a lesser extent by nutrition. However, it seems that carbohydrate and protein intakes have equal importance.

Liraglutide for overweight and obesity

Liraglutide for overweight and obesity

Energy Expenditure Following Spinal Cord Injury: A Delicate Balance.

Following a spinal cord injury (SCI), neurogenic obesity results from changes in body composition, physical impairment, and endometabolic physiology and when dietary intake exceeds energy expenditure. Given the postinjury reductions in lean body mass, sympathetic nervous system dysfunction, and anabolic deficiencies, energy balance is no longer in balance, and thereby an obesogenic environment is created that instigates cardiometabolic dysfunction. Accurate determination of metabolic rate can prevent excess caloric intake while promoting positive body habitus and mitigating obesity-related comorbidities. Metabolic rate as determined by indirect calorimetry (IC) has not been adopted in routine clinical care for persons with SCI despite several studies indicating its importance. This article reviews current literature on measured and predicted metabolic rate and energy expenditure after SCI and stresses the importance of IC as standard of care for persons with SCI.

The Effects of Very Low Energy Diets and Low Energy Diets with Exercise Training on Skeletal Muscle Mass: A Narrative Review.

In recent years, very-low-energy diets (VLEDs) have been recognised as a viable strategy for improving the extent of weight loss and cardio-metabolic outcomes in people who are either overweight or obese. However, concerns exist regarding the reductions in lean body mass (LBM) during VLEDs, particularly in vulnerable demographic groups, such as middle-aged and older adults already prone to developing sarcopenia. Sarcopenia is itself associated with multiple adverse outcomes, including frailty, cardio-metabolic deterioration and increased mortality. Therefore, a number of studies investigating strategies to ameliorate this detrimental effect of VLEDs have attempted to address this concern. This narrative review explores the potential benefits and limitations of exercise and/or protein supplementation for LBM retention during VLEDs based on the available evidence. Current studies suggest that both protein supplementation and exercise training may result in improved LBM retention (and skeletal muscle function) during VLEDs. However, uncertainty remains concerning the interactions between intervention types, based on discordant outcomes reported in the literature and the heterogeneity of exercise modalities in achieving this particular outcome.

Prolonged fasting induces long-lasting metabolic consequences in mice

To endure prolonged fasting, animals undergo important acute physiological adjustments. However, whether severe fasting also leads to long-term metabolic adaptations is largely unknown. Forty-eight-hour fasting caused a pronounced weight loss in adult C57BL/6 male mice. Seven days of refeeding increased body adiposity to levels above baseline, whereas fasting-induced reductions in lean body mass and energy expenditure were not fully recovered. Respiratory exchange ratio and locomotor activity also remained altered. A fasting/refeeding cycle led to persistent suppression of Pomc mRNA levels and significant changes in the expression of histone deacetylases and DNA methyltransferases in the hypothalamus. Additionally, histone acetylation in the ventromedial nucleus of the hypothalamus was reduced by prolonged fasting and remained suppressed after refeeding. Mice subjected to 48-h fasting 30 days earlier exhibited higher body weight and fat mass compared to aged-matched animals that were never food-deprived. Furthermore, a previous fasting experience altered the changes in body weight, lean mass, energy expenditure and locomotor activity induced by a second cycle of fasting and refeeding. Notably, when acutely exposed to high-palatable/high-fat diet, mice that went through cumulative fasting episodes presented higher calorie intake and reduced energy expenditure and fat oxidation, compared to mice that had never been subjected to fasting. When chronically exposed to high-fat diet, mice that experienced cumulative fasting episodes showed higher gain of body and fat mass and reduced energy expenditure and calorie intake. In summary, cumulative episodes of prolonged fasting lead to hypothalamic epigenetic changes and long-lasting metabolic adaptations in mice.

Changes in Whole-Body Amino Acid Metabolism in Response to 2 Weeks of the Very-Low Calorie Diet Are Not Affected by Gender

Abstract Objectives Very Low-Calorie Diet (VLCD) is an approved method to safely achieve substantial short-term weight loss in obese patients. We previously reported that two weeks of the VLCD maintains whole-body protein and amino acid turnover despite a large reduction in lean body mass. Since the observed effects on body weight (BW) and composition differed between men and women, we hypothesized that the changes in amino acid metabolism in a response to the calorie-restricted diet is gender-specific. Methods 34 morbidly obese adults (BMI: 42 ± 0.9 kg/m2, 10 males and 24 females) underwent a VLCD for 2 weeks consisting of 820 kcal/day and 105-grams protein/day. Before the start of the VLCD (baseline), the whole-body production (WBP) rates of multiple amino acids involved in protein metabolism (e.g., glycine (GLY), glutamine (GLN), phenylalanine (PHE), tyrosine (TYR), and arginine (ARG)) were measured after IV pulse administration of their stable isotopes. Weight loss and body composition by dual-energy X-ray absorptiometry were assessed after 2 weeks of the VLCD. Baseline plasma enrichments were measured by LC-MS/MS. Data are presented as mean ± SE. Statistics are performed by Pearson correlation tests. Results The magnitude of the BW loss after 2 weeks of the VLCD differed between males and females (7.0 ± 0.7 kg vs. 4.1 ± 0.2 kg, P &amp;lt; 0.0001, respectively) with a higher reduction in lean body mass observed in men than women (4.3 ± 0.8 kg vs. 2.7 ± 0.4 kg, P &amp;lt; 0.05). Although, females had significantly reduced baseline WBP of ARG (7.3% vs. 2%, P = 0.0027), GLY (22.8% vs. 3.6%, P &amp;lt; 0.001), and PHE (4.8% vs. 3.1%, P = 0.018) in comparison to men, two weeks of the VLCD had a comparable effect on multiple amino acid WBP in both genders. Suppressed contractile myofibrillar protein breakdown rate was observed in both groups (13% vs. baseline, P = 0.02) with no gender difference in net protein breakdown (PHE to TYR conversion rate). Hence, increased catabolism in men cannot be explained by a different response to the 2 weeks of a calorie-restricted diet. Conclusions Despite gender differences in body weight loss and changes in composition in response to a Very Low-Calorie Diet, changes in whole-body amino acid kinetics are not differently affected in men and women. Funding Sources CTRAL Internal Funds.