Increased Fat Mass Research Articles

Assessment of body composition in young adulthood and its associations to early changes in cardiovascular phenotypes: a cross-sectional study

Abstract Introduction Obesity in young adulthood is associated with various cardiovascular structural and functional changes, commonly used as markers of early subclinical cardiovascular disease. Whether these changes occur predominantly in relation to increased fat mass (FM) or are instead more closely related to simultaneous increases in underlying fat-free mass (FFM) that are known to occur in obesity, is incompletely understood. Purpose To investigate associations between both FM and FFM and a wide range of cardiac (left ventricular mass, LVM; end-diastolic volume, EDV; cardiac output, CO; stroke volume, SV), vascular (systolic blood pressure, SBP; diastolic blood pressure, DBP; mean arterial pressure, MAP; systemic vascular resistance, SVR) and autonomic (heart rate variability triangular index, HRVTI; baroreceptor reflex sensitivity, BRS) phenotypes commonly used to monitor the early evolution of subclinical CVD. Methods The study used data from extensive adipose and cardiovascular phenotyping of 408 healthy young adults (mean age 21 years) participating in a sub-study of the long-running ALSPAC birth cohort. We performed cross-sectional analysis using multiple imputation, multivariable linear regression and interaction testing to assess the association between both FM and FFM and cardiovascular phenotypes. Results Our study revealed that FFM resulted in a much greater increase in CO (difference in outcome per 1-SD difference in exposure β=0.58L/min, p<0.01, 95% CI=0.38, 0.77) than FM (β=0.20L/min, p=0.01, 95% CI=0.05, 0.36), following adjustment for both tissue types. FFM was also associated with an increase in LVM (β=19.1g, p<0.01, 95% CI=16.61, 21.58), EDV (β=22ml, p<0.01, 95% CI=18.18, 25.13) and SV (β=13ml, p<0.01, 95% CI=10.96, 15.75). FFM was also associated with improved autonomic and peripheral vascular function, including lower HR (β=-4bpm, p<0.01, 95% CI=-6.12, -1.95), higher HRVTI (β=2.1, p<0.01, 95% CI=0.72, 3.48) and lower SVR (β=-1.1, p<0.01, 95% CI=-2.12, -1.07), resulting in unchanged MAP despite elevations in CO. On the contrary, FM was not associated with LVM (β=-0.91g, p=0.35, 95% CI=-2.85, 1.02), and was associated with lower EDV (β=-4.62ml, p<0.01, 95% CI=-7.34, -1.88) and reduced autonomic function, as seen with HRVTI (β=-1.83, p<0.01, 95% CI=-3.02, -0.64) and BRS (β=-2.47, p=0.01, 95% CI=-4.27, -0.67). FM was also associated with increased HR (β=3.26bpm, p<0.01, 95% CI=1.57, 4.94) and increased SBP (β=2.14mmHg, p<0.01, 95% CI=1.01, 3.27) DBP (β=2.68mmHg, p<0.01, 95% CI=1.60, 3.77), and MAP (β=2.34mmHg, p<0.01, 95% CI=1.34, 3.34). Conclusion In young adults, changes in surrogate clinical markers of cardiac, vascular, and autonomic function commonly attributed solely to increases in fat mass should be interpreted with caution as they may be associated with underlying changes in FFM. Future work should focus on longitudinal studies of this cohort to confirm remodelling patterns based on these clinical markers.

Fat mass mediating effect on the association of worsening insulin resistance with increased left ventricular mass in 1595 adolescents: a 7-Year Longitudinal and Mediation Study

Abstract Background Fat mass-insulin resistance vicious cycle has been established in the young population and late adolescence has been identified as the critical time when the pathologic cycle begins. However, the independent and synergistic effect of fat mass in the relationship of insulin resistance with cardiac structure remains unexamined in a large cohort of adolescents, possibly due to the scarcity of repeated echocardiography measures. Mounting effective prevention strategies relies on strong evidence of the timing of the earliest cardiovascular alteration induced by insulin resistance. Purpose To investigate the longitudinal association of insulin resistance with left ventricular mass (LVM) and the mediating effect of fat mass in adolescents. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting glucose and insulin measured at 17- and 24-year clinic visits were included. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated from fasting insulin x fasting glucose/22.5 at ages 17 and 24 years. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7) was available at baseline and follow-up. Fat mass was repeatedly measured with dual-energy Xray absorptiometry at both time points. Multivariable adjusted association was examined using generalized linear mixed-effect models and adjusted for sex, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, and time-varying covariates measured at both baseline and follow-up such as age, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol. Mediation analysis was conducted with a structural equation model adjusting for same covariates, except fat mass. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median insulin resistance increased from 1.46 to 1.74, median fat mass increased from 15.6kg to 19.2kg and the mean LVMI increased from 35.4g/m2.7 to 38.1g/m2.7, over 7 years. In a fully adjusted model, increased insulin resistance from adolescence through young adulthood was significantly associated with increased LVMI (effect estimate 1.01g/m2.7 [95% CI, 0.63 – 1.57], p<0.001) across the 7-year observation period. Increased fat mass mediated (62.3% mediation effect) the longitudinal association between insulin resistance and LVMI from ages 17 – 24 years. Conclusion Worsening insulin resistance from adolescence through young adulthood was associated with increased cardiac mass, contributing 37% to the total increase in LVMI between ages 17 to 24 years but increased fat mass explained two-thirds of the relationship.

Effect of Fontan circulation on body composition and correlation with exercise capacity

Abstract Background There is growing attention to body composition in Fontan patients (FP) and preliminary results suggest that FP have an increased fat mass and a decreased muscle mass compared to the healthy population. FP also have reduced exercise capacity compared to health peers. However, data are still limited. Purpose The aim of our study was to compare the body composition (BC) of adult patients with Fontan circulation and healthy controls and to assess the correlation with functional capacity. Material and Methods Case control study on adult patients with Fontan circulation (FP) and age and gender matched healthy controls (HC). The following characteristics were recorded: age, gender, morphology of the systemic ventricle, type of Fontan circulation, level of physical activity (PAR, 0-7 points, 0 = sedentary - 7 = running > 3hours/week). S-score muscle, T-score bone, fat mass (FM%), intra-muscular adipose tissue (IMAT), abdominal adipose tissue (AAT), intracellular water (ICW), extracellular water (ECW), total body water (TBW), were measured through multi-frequency bioelectrical impedance technology in the FP and in the HC. Correlation was made for FP between body composition and oxygen consumption at peak exercise (VO2 peak), VE/VCO2 slope and NYHA class as indicator of functional capacity. Results Thirty Fontan patients (FP, mean age 24±6 yrs, 70% males) and 30 matched healthy controls (HC) were recruited in the study. The systemic ventricle was dominant left in 14 patients (47%), dominant right in 16 (53%). Four patients had atrio-pulmonary connection, the remaining were palliated with a lateral tunnel (n=26, 87%). The analysed parameters are summarised in Table 1. PAR was reduced in FP compared to HC (median 4.0 points in FP versus 7.0 points in HC, p 0.024). There was no difference in the BMI, fat mass, and body water between FP and HC. However, FP showed significantly lower S and T scores compared to the HC (S-score: -0,75 in FP versus 0,0 in HC, p 0.003. T-score: -0.9 in FP versus -0.25 in HC, p 0.001). In FP, NYHA Class was I in 28 patients (93%), II in 1 (3,5%) and III in 1 (3.5%) patient. The mean VO2 was 23.4±5.4mlO2/kg/min and mean VE/VCO2 slope 32±7. There was a direct correlation between VO2 peak and the PAR (rho 0.443, p 0.044). No correlation was found between the VO2 peak, the VE/VCO2 slope or the NYHA Class and the analysed parameters of body composition. Conclusion FP have reduced muscle mass, and bone density compared to HC. In addition to the known reduced efficiency of the cardiac pump during exercise in FP, the lower level of conditioning contributes to the reduced exercise capacity in this population. Programs aiming to encourage physical activity are key and should be part of patients’ care.

Quercetin supplementation in metabolic syndrome: nutrigenetic interactions with the Zbtb16 gene variant in rodent models

BackgroundQuercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16).ResultsQuercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q.ConclusionQuercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

Nutrition and Physical Activity in Older Adults with CKD patients: Two Sides of the Same Coin.

Nutrition and physical activity are two major issues in the management of CKD patients who are often older, have comorbidities and are prone to malnutrition and physical inactivity, conditions that cause loss of quality of life and increase the risk of death. We performed a multidimensional assessment of nutritional status and of physical performance and activity in CKD patients on conservative therapy in order to assess the prevalence of sedentary behaviour and its relationship with body composition. 115 consecutive stable CKD patients aged 45-80 years were included in the study. They had no major skeletal, muscular or neurological disabilities. All patients underwent a multidimensional assessment of body composition, physical activity and exercise capacity. Sedentary patients, as defined by mean daily METs < 1.5 were older and differed from non-sedentary patients in terms of body composition, exercise capacity and nutrient intake, even after adjusting for age. Average daily METs were positively associated with lean body mass, muscle strength, 6-MWT performance, but negatively associated with fat body mass, body mass index and waist circumference. In addition, a sedentary lifestyle may have negative effects on free fat mass, muscle strength and exercise capacity, and may increase fat body mass. Conversely, s decrease in muscle mass and/or an increase in fat mass may lead to a decrease in physical activity and exercise capacity. There is a clear association and potential interrelationship between nutritional aspects and exercise capacity in older adults with CKD: they are really the two sides of the same coin.

Effects of Environmental Noise Stress on Mouse Metabolism

Environmental noise is associated with various health outcomes. However, the mechanisms through which these outcomes influence behavior and metabolism remain unclear. This study investigated how environmental noise affects the liver, adipose tissue, and brain metabolic functions, leading to behavioral and body weight changes. Mice were divided into a noise group exposed to construction noise and an unexposed (control) group. Behavior and body weight changes were monitored over 50 days. Early changes in response to noise exposure were assessed by measuring plasma cortisol and glial fibrillary acidic protein expression in brain tissues on days 1, 15, and 30. Chronic responses, including changes in lipoprotein and fat metabolism and neurotransmitters, were investigated by analyzing serum lipoprotein levels and body fat mass and evaluating liver, fat, and brain tissue after 50 days. The noise group showed higher locomotor activity and reduced anxiety in the open-field and Y-maze tests. Noise exposure caused an initial weight loss; however, chronic noise increased fat mass and induced adipocyte hypertrophy. Our findings underscore the role of environmental noise-induced stress in augmenting locomotor activity and reducing anxiety in mice through neurotransmitter modulation while increasing the risk of obesity by decreasing HDL cholesterol levels and promoting adipocyte hypertrophy.

8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study

Abstract Disclosure: A.O. Agbaje: None. Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p<0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p<0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p<0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p<0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood. Presentation: 6/1/2024

The endocrine manifestations of adults with spinal muscular atrophy.

Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA. The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30-51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated. In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM. Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.

7769 Natural plant extract alleviates high-fat diet-induced obesity through enhancing PLIN5 expression

Abstract Disclosure: S. Shin: None. H. Jang: None. E. Kwon: None. Obesity is one of the metabolic diseases caused by excessive differentiation and excessive accumulation of adipose tissue due to an imbalance between energy intake and consumption. Various drugs have been developed to effectively treat obesity, but the side effects often outweigh the benefits. Therefore, alternative weight loss supplements that can minimize side effects are needed. In this study, the effects of natural plant extract (NPE) on the high-fat diet (HFD)-induced obesity mice were confirmed to discover new anti-obesity material.After acclimating C57BL/6J mice for 1 week, they were divided into two groups: a normal diet (ND) group and an HFD group. After inducing obesity over 4 weeks, the HFD group was divided into HFD and HFD+NPE and reared together with the ND group for an additional 10 weeks. After a 12-hour fasting period, observations were made on weight, adipose tissue mass, morphological changes in adipocytes, and the expression differences in genes and proteins related to fatty acid oxidation (FAO) in the epididymal white adipose tissue, particularly focusing on the PLIN5 protein.The increase in body weight and epididymal fat mass induced by the HFD was reduced by the administration of NPE. Morphological analysis of the epididymal fat revealed a significant increase in adipocyte size in the HFD group, whereas the NPE group showed a reduction in adipocyte size. The expression of FAO-related genes (PPARa, PGC1a, CPT1, and CPT2) and TCA cycle-related genes (PDHb, ACO, DIST, SUCLG, SDHC, and MDH2) decreased in the epididymal fat due to the HFD, but significantly increased with the administration of NPE. The NPE induced the breakdown of intracellular stored triglycerides by upregulating ATGL, LIPE, and MGL mRNA expression. The resulting liberated fatty acids were translocated to the mitochondria and oxidized through the TCA cycle, ultimately leading to a reduction in body fat. Furthermore, PLIN5 expression exhibited a significantly higher level in the NPE group compared to the other two groups. In other words, elevation in PLIN5 expression, induced by the NPE, appears to enhance lipid breakdown, activate FAO pathways, and stimulate the TCA cycle. Consequently, lipid combustion is increased, improving the weight gain and fat accumulation induced by the HFD.If additional experimental results on human application align with the above findings, NPE holds the potential as a low-side-effect ingredient for weight loss supplements. Presentation: 6/1/2024

Differences in sarcopenia indices in elderly Japanese women and their relationships with obesity classified according to waist circumference, BMI, and body fat percentage

BackgroundSarcopenic obesity (SO) is defined as a decrease in lean body mass and an increase in body fat mass (BFM) due to aging. Detecting SO in elderly women is important from the perspective of extending healthy life expectancy. While various indices of SO are currently used, there is no global consensus regarding diagnostic criteria for SO. This study aimed to examine the relationship between obesity indices (waist circumference (WC), body mass index (BMI), and body fat percentage (BFP)) and sarcopenia indices (total body muscle mass (TBM), appendicular lean mass (ALM), skeletal mass index (SMI)), and physical function (gait speed (GS), handgrip strength (HGS)).MethodsSubjects were 170 community-dwelling healthy elderly women aged 65–79 years (mean: 72.7 ± 5.78 years) who underwent measurements for WC, BMI, and BFP. A WC of ≥ 90cm was defined as the obese group, BMI was determined as weight (kg) divided by height squared (m2) and a cutoff of ≥ 25 kg/m2 was used to define the obesity group. BFM was measured using the bioelectrical impedance analysis (BIA) method and BFP was calculated from body weight and a cutoff of ≥ 30% was used to define the obesity group. TBM and ALM (kg) were measured using the BIA method, ALM (kg) was corrected for height (m2) to obtain SMI (kg/m2). Physical function was assessed by GS and HGS, which were measured by the 5-m walk test and a digital grip strength meter, respectively.ResultsWhen obesity was assessed using BMI, WC and BFP, obese individuals had higher TBM, ALM and SMI, and lower GS among the sarcopenia indicators. HGS did not differ significantly between the non-obese and obese groups.ConclusionOur findings suggest HGS is thought to reflect muscle strength without being affected by obesity indices, suggesting that it may be useful in detecting possible sarcopenia in obese individuals.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Greater energy surplus promotes body protein accretion in healthy young men: A randomized clinical trial

Background & aimsCaloric overfeeding combined with adequate protein intake increases not only body fat mass but also fat-free mass. However, it remains unclear whether the increase in fat-free mass due to overfeeding is associated with an increase in total body protein mass. We evaluated the hypothesis that overfeeding would promote an increase in total body protein mass. MethodsIn our randomized controlled trial, 23 healthy young men were fed a diet equivalent to their energy requirements with a +10 % energy surplus from protein alone or a +40 % energy surplus (+10 % from protein, +30 % from carbohydrate) for 6 weeks. We estimated total body protein mass by a four-compartment model using dual-energy X-ray absorptiometry, deuterium dilution, and hydrostatic underwater weighing. ResultsThe 40 % energy surplus over 6 weeks significantly increased body protein mass compared to baseline by 3.7 % (0.44 kg; 95 % confidence interval [CI], 0.21–0.67 kg; P = 0.003); however, the 10 % energy surplus did not result in a significant change (0.00 kg; 95 % CI, −0.38–0.39 kg; P = 0.980). A significant interaction between intervention duration (time) and energy surplus (group) was observed for total body protein mass (P = 0.035, linear mixed-effects model), with a trend toward a significant difference in total body protein mass gain between groups (P = 0.059, Wilcoxon rank sum test). The increase in body protein mass due to the energy surplus was correlated with an increase in fat mass (r = 0.820, p = 0.002). ConclusionsA higher energy intake was found to promote an increase in body protein mass in healthy men consuming excess protein, suggesting the importance of energy surplus in body protein accumulation. This effect of energy surplus may be related to factors such as increased body fat mass and the associated secretion of adipokines. Trial registrationThe trial was registered with the University Hospital Medical Information Network Clinical Trial Registry as UMIN000034158.

IGF-1 and insulin receptors in LepRb neurons jointly regulate body growth, bone mass, reproduction, and metabolism.

Leptin receptor (LepRb)-expressing neurons are known to link body growth and reproduction, but whether these functions are mediated via insulin-like growth factor 1 receptor (IGF1R) signaling is unknown. IGF-1 and insulin can bind to each other's receptors, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we created mice lacking IGF1R exclusively in LepRb neurons (IGF1RLepRb mice) and simultaneously lacking IGF1R and insulin receptor (IR) in LepRb neurons (IGF1R/IRLepRb mice) and then characterized their body growth, bone morphology, reproductive and metabolic functions. We found that IGF1R and IR in LepRb neurons were required for normal timing of pubertal onset, while IGF1R in LepRb neurons played a predominant role in regulating adult fertility and exerted protective effects against reproductive aging. Accompanying these reproductive deficits, IGF1RLepRb mice and IGF1R/IRLepRb mice had transient growth retardation. Notably, IGF1R in LepRb neurons was indispensable for normal trabecular and cortical bone mass accrual in both sexes. These findings suggest that IGF1R in LepRb neurons is involved in the interaction among body growth, bone development, and reproduction. Though only mild changes in body weight were detected, simultaneous deletion of IGF1R and IR in LepRb neurons caused dramatically increased fat mass composition, decreased lean mass composition, lower energy expenditure, and locomotor activity in both sexes. Male IGF1R/IRLepRb mice exhibited impaired insulin sensitivity. These findings suggest that IGF1R and IR in LepRb neurons jointly regulated body composition, energy balance, and glucose homeostasis. Taken together, our studies identified the sex-dependent complex roles of IGF1R and IR in LepRb neurons in regulating body growth, reproduction, and metabolism.

Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis

Erythropoietin (EPO) plays a key role in energy metabolism, with EPO receptor (EpoR) expression in white adipose tissue (WAT) mediating its metabolic activity. Here, we show that male mice lacking EpoR in adipose tissue exhibit increased fat mass and susceptibility to diet-induced obesity. Our findings indicate that EpoR is present in WAT, brown adipose tissue, and skeletal muscle. Elevated EPO in male mice improves glucose tolerance and insulin sensitivity while reducing expression of lipogenic-associated genes in WAT, which is linked to an increase in transcription factor RUNX1 that directly inhibits lipogenic genes expression. EPO treatment in wild-type male mice decreases fat mass and lipogenic gene expression and increase in RUNX1 protein in adipose tissue which is not observed in adipose tissue EpoR ablation mice. EPO treatment decreases WAT ubiquitin ligase FBXW7 expression and increases RUNX1 stability, providing evidence that EPO regulates energy metabolism in male mice through the EPO-EpoR-RUNX1 axis.

The relationship between diabetes mellitus and non-alcoholic fatty liver disease: a clinical and instrumental paired study

To study the impact of type 2 diabetes mellitus (DM2) on the severity of liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). To conduct a paired case-control study 2989 patients were examined at the Federal Research Center of Nutrition, Biotechnology and Food Safety. Pairs were matched by gender and age and distributed into groups: NAFLD + DM2+ (n=313), NAFLD + DM2- (n=313) and a control group of patients without NAFLD and without DM2 (n=313). The severity of liver steatosis was determined by measuring the controlled attenuation parameter. The severity of liver fibrosis was determined by measuring the liver stiffness measurement. Body composition of the patients was determined using bioimpedance measurements. Indicators of lipid and carbohydrate metabolism, and the serum activity of liver enzymes was determined by standard biochemical methods. In NAFLD + DM2+ group compared to NAFLD + DM2- group, and in NAFLDM + DM2-compared to the control group, weight, BMI, waist and hip circumference, waist-to-hip ratio were higher, while in all. In NAFLD + DM2+ and NAFLD + DM2- groups the volume of fat mass directly correlated with the level of blood triglycerides (r=0.21), HbA1с (r=0.32) and fasting blood glucose (r=0.35), and inversely correlated with high-density lipoproteins (r=-0.19). In NAFLD + DM2+ group versus NAFLD + DM2- group severe steatosis (S3, 78% versus 59.4%; p<0.001) and severe fibrosis (F4, 8% vs 2.6%; p<0.001) was more common; 70% of patients in the NAFLD + DM2- group had no liver fibrosis according to elastography (F0), while in the NAFLD + DM2+ group only 43.2% of patients had no liver fibrosis (p<0.0001). When NAFLD is accompanied by DM2, there is an increase in total fat mass, the severity of steatosis and liver fibrosis, and an associated deterioration of lipid metabolism. More than half of these patients have various stages of liver fibrosis, which indicates the progressive nature of the disease.

Effects of Heat Stress-Induced Sex Hormone Dysregulation on Reproduction and Growth in Male Adolescents and Beneficial Foods.

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2-6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.

The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.

Dietary and Lifestyle Management of Functional Hypothalamic Amenorrhea: A Comprehensive Review.

Functional Hypothalamic Amenorrhea (FHA) is a condition characterized by the absence of menstruation, which is increasingly affecting young women. However, specific recommendations for treating and preventing this condition are lacking. Based on a review of the available literature, this article provides practical and feasible dietary management recommendations for healthcare professionals and researchers in women's health and nutrition. It answers the question of what interventions and nutritional recommendations are necessary to restore menstrual function in women struggling with FHA. Physicians recommend an energy availability threshold of 30 kcal/kg FFM/day to prevent FHA. Also, energy availability below and above this threshold can inhibit LH pulsation and cause menstrual disorders. In addition, the risk of menstrual disorders increases with a decrease in the caloric content of the diet and the duration of the energy deficit, and women with FHA have significantly lower energy availability than healthy women. It is essential to ensure that adequate kilocalories are provided throughout the day (regular meals that are a source of proper glucose) to avoid a negative energy balance, as glucose has been proven to affect LH pulses and T3 and cortisol concentrations in the body. Dietary intervention should focus on increasing the caloric content of the diet, thus increasing energy availability and restoring energy balance in the body. Treatment and diagnosis should also focus on body composition, not just body weight. An increase in body fat percentage above 22% may be required to restore menstrual function. In women with FHA, even an increase in body fat mass of one kilogram (kg) increases the likelihood of menstruation by 8%. It is advisable to reduce the intensity of physical activity or training volume, while it is not advisable to give up physical activity altogether. It is also important to ensure adequate intake of micronutrients, reduce stress, and incorporate cognitive-behavioral therapy.

The Effectiveness of Physical Activity Intervention at School on BMI and Body Composition in Overweight Children: A Pilot Study

(1) Background: Overweight children usually have lower levels of physical activity (PA) than their normal-weight peers. Low PA predisposes to an increase in body fat mass. The aim of this study was to evaluate the effectiveness of school-based PA intervention on the anthropometric indicators and body composition of overweight and obese children during a two-year observation period, from the age of 10 to 12. (2) Materials and methods: The research included 148 children with overweight or obesity who were born in 2007. There were two groups of children with standard and elevated PA at school (SPA and EPA; 4 and 10 h of physical education lessons a week, respectively). Anthropometric and body composition measurements were carried out. Body mass index (BMI), fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM), and total body water (TBW) were estimated. In total, five measurements were conducted at intervals of 5–6 months. (3) Results: In EPA group, the percentage of obese children decreased from 46% to 35.25%, and in SPA group, this percentage increased from 42.75% to 46%. Only 3.33% of children in the standard PA group (one child) and 17.2% in the elevated PA group (six children) changed their BMI and FM categories from overweight to normal body mass. In EPA children, FM decreased from 28.65% to 26.41%, and in SPA children, it increased from 30.31% to 31.75%. The highest increase in FFM was in EPA boys, while SPA boys recorded the highest decrease. In SPA children, SMM increased by 0.43% from 38.85% to 39.28%, and in EPA children, it increased by 2.51% from 40.27% to 42.78%. In EPA children, TBW slightly increased from 53.26% to 53.59%, and in SPA children, it decreased from 50.70% to 49.93%. (4) Conclusions: Elevated PA at school has a positive effect on the BMI and body composition of children who are overweight or obese. Increasing the mandatory number of physical education lessons in school curricula is an efficient strategy for reducing obesity in school-aged children.

Cold Exposure Rejuvenates the Metabolic Phenotype of Panx1-/- Mice.

Pannexin1 (Panx1) ATP channels are important in adipocyte biology, potentially influencing energy storage and expenditure. We compared the metabolic phenotype of young (14 weeks old) and mature (20 weeks old) wild-type (WT) and Panx1-/- mice exposed or not to cold (6 °C) during 28 days, a condition promoting adipocyte browning. Young Panx1-/- mice weighed less and exhibited increased fat mass, improved glucose tolerance, and lower insulin sensitivity than WT mice. Their energy expenditure and respiratory exchange ratio (RER) were increased, and their fatty acid oxidation decreased. These metabolic effects were no longer observed in mature Panx1-/- mice. The exposure of mature mice to cold exacerbated their younger metabolic phenotype. The white adipose tissue (WAT) of cold-exposed Panx1-/- mice contained more small-sized adipocytes, but, in contrast to WT mice, white adipocytes did not increase their expression of Ucp1 nor of other markers of browning adipocytes. Interestingly, Glut4 expression was already enhanced in the WAT of young Panx1-/- mice kept at 22 °C as compared to WT mice. Thus, Panx1 deletion exerts overall beneficial metabolic effects in mice that are pre-adapted to chronic cold exposure. Panx1-/- mice show morphological characteristics of WAT browning, which are exacerbated upon cold exposure, an effect that appears to be associated with Ucp1-independent thermogenesis.