Increased Body Fat Mass Research Articles

Growth hormone deficiency in adults with hypopituitarism-What are the risks and can they be eliminated by therapy?

Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. Many of the features associated with GH deficiency in adults improve, or even normalize, and the safety profile is reassuring. The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.

Eating architecture in adults at increased risk of type 2 diabetes: associations with body fat and glycaemic control.

Eating architecture is a term that describes meal frequency, meal timing and meal size and the daily variation in each of these. The aim of this study was to determine the relationship between components of eating architecture on body fat and markers of glycaemic control in healthy adults at increased risk of type 2 diabetes (T2DM). Participants (n 73, 39 males, age 58·8 (8·1) years, BMI 33·4 (4·4) kg/m2) recorded food intake and wore accelerometers and continuous glucose monitors (CGM) for 7-14 d under free-living conditions. Body fat and glycated Hb (HbA1c) were also measured. The mean and day-to-day variation (calculated as the standard deviation during the monitoring period) of each component of eating architecture were calculated. Multivariable linear regression models were constructed for three separate outcome variables (body fat mass, mean CGM glucose and HbA1c) for each component of eating architecture before and after adjustment for confounders. Higher variability in the time of first meal consumption was associated with increased body fat mass after adjusting for confounders (β = 0·227, 95 % CI: 0·019, 0·434, P = 0·033). Increased variability in the time lag from waking to first meal consumption was also positively associated with increased HbA1c after adjustment (β = 0·285, 95 % CI: 0·040, 0·530, P = 0·023). Low day-to-day variability in first meal consumption was associated with lower body fat and improved glucose control in adults at increased risk of T2DM. Routine consumption of meals may optimise temporal regulation to anticipate and respond appropriately to a glucose challenge.

The mediatory role of inflammatory markers on the relationship between dietary energy density and body composition among obese and overweight adult women: A cross‐sectional study

Energy density (ED) is known to influence body composition (BC). Indeed, consumption of high ED foods can increase body fat mass (BFM) and inflammatory markers. We sought to assess the mediatory role of high-sensitive-C-reactive protein (hs-CRP), transforming growth factor-β (TGF-beta), and plasminogen activator inhibitor-1 (PAI-1) on the relationship between ED and BC in women with overweight/obesity. This was a cross-sectional study consisting of 391 women. Body composition (Bioelectrical Impedance Analysis) and a food frequency questionnaire (FFQ) was used to assess the BC and food intake of individuals. Blood samples and serum level of hs-CRP, PAI-1, and TGF-β were collected. ED per one gram of foods was calculated and divided to quartiles. Linear logistic regression was used to investigate the association between BC across quartiles of ED intake. Total body water (TBW), fat free mass (FFM), visceral fat area (VFA), and fat free mass index (FFMI) appeared to be mediated by hs-CRP across ED quartiles. TBW, FFM with PAI-1, bone mineral content (BMC) with PAI-1 and TGF-beta, and skeletal lean mass (SLM) were inversely associated with hs-CRP, respectively. Fat trunk, TBW, BFM, FFM, SLM, waist circumference (WC), FFMI, and FMI were positively mediated by TGF-beta with increasing ED food intakes. Fat trunk, BFM, SLM, WC, FFMI and FMI were positively mediated by PAI-1. Most BC subcategories were positively associated with higher ED intake, mediated by increasing serum levels of PAI-1 and TGF-beta. Moreover, higher serum hs-CRP levels may be related to body fat and water alteration concomitant to a higher ED intake.

Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective.

Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerance vs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection with M. tuberculosis (Mtb) H37Rv after the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-α, IFN-γ, IFN-β and IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association.

Characterization of the onset of leptin effects on the regulation of energy balance.

Leptin is a hormone required for the regulation of body weight in adult animals. However, during the postnatal period, leptin is mostly involved in developmental processes. Because the precise moment at which leptin starts to exert its metabolic effects is not well characterized, our objective was to identify the approximate onset of leptin effects on the regulation of energy balance. We observed that male Lepob/ob mice started to exhibit increased body fat mass from postnatal day 13 (P13), whereas in females, the increase in adiposity began on P20. Daily leptin injections from P10 to P22 did not reduce the weight gain of WT mice. However, an acute leptin injection induced an anorexigenic response in 10-day-old C57BL/6 mice but not in 7-day-old mice. An age-dependent increase in the number of leptin receptor-expressing neurons and leptin-induced pSTAT3 cells was observed in the hypothalamus of P7, P10 and P16 mice. Leptin deficiency started to modulate the hypothalamic expression of transcripts involved in the regulation of metabolism between P7 and P12. Additionally, fasting-induced hypothalamic responses were prevented by leptin replacement in 10-day-old mice. Finally, 12-day-old males and females showed similar developmental timing of axonal projections of arcuate nucleus neurons in both WT and Lepob/ob mice. In summary, we provided a detailed characterization of the onset of leptin's effects on the regulation of energy balance. These findings contribute to the understanding of leptin functions during development.

Disruption of Adipose Tissue Metabolism by Glucocorticoids Is Attenuated With LXRβ Antagonism

Excessive exposure to glucocorticoids (GCs), either from endogenous overproduction of cortisol, or exogenous pharmacological GC treatment, potentiates the development of diabetes and obesity in a fat depot-specific manner. Undesirable metabolic side effects resulting from the activation of the glucocorticoid receptor (GR) remain a key limitation to the long-term therapeutic use of GCs as immunosuppressants. GC treatment disrupts the thermogenic function of brown adipose tissue (BAT) and enhances futile cycling within white adipose tissue (WAT). Mice lacking the liver X receptors (LXRs) were previously shown to have smaller AT depots with enhanced BAT activity compared to wildtype (WT) mice. We previously demonstrated that LXRβ is required to mediate the side effects of GCs in the liver but not the beneficial anti-inflammatory effects of GCs. The discovery of this GC/LXRβ cross-talk led to the hypothesis that LXRβ antagonism may be therapeutically beneficial to prevent GC-induced dysfunction in AT. To test this idea, LXRα-/- mice were treated for 5 days with vehicle, 5 mg/kg dexamethasone (Dex, a synthetic GC agonist), and/or 40 mg/kg GSK2033 (GSK, non-selective LXR antagonist). As expected, Dex-treated mice showed significant accumulation of lipids in BAT and were unable to maintain their body temperature when exposed to cold, yet GSK was able to protect against these effects. Dex increased body fat mass and caused adipocyte enlargement in WAT which was not observed in mice co-treated with GSK. At the transcriptional level, GSK attenuated Dex-mediated downregulation of thermogenic genes in BAT, and upregulation of lipogenic genes in WAT. Similar beneficial changes were confirmed in WT mice. The protection afforded by GSK against Dex-induced fat accumulation was confirmed to be cell-autonomous from studies in adipose-specific LXRβ-/- mice (AdβKO). Dex-dependent increases in lipolysis in gonadal WAT and plasma free fatty acids (FFA) were also attenuated by GSK co-treatment. With GSK co-treatment, Dex-induced liver steatosis was diminished suggesting that LXRβ antagonism attenuated FFA shuttling to the liver. The lipolytic and lipotoxic effects of Dex in AT and liver were largely abrogated in AdβKO along with improved systemic insulin sensitivity. Overall, our data suggest that LXRβ antagonism prevents disruption of BAT and WAT (and indirectly liver) function caused by GC treatment in an in vivo model, highlighting the potential role of LXRβ antagonists in combating the negative effects of excessive GC exposure on the development of diabetes and obesity. The identification of this novel mechanism of interrupting GC adipose tissue action suggests therapeutic targeting of LXRβ with an antagonist could improve the health of patients currently taking GCs to control inflammation but suffer the detrimental side effects of drug treatment.

The role of laparoscopic sleeve gastrectomy on inflammatory parameters in morbidly obese patients.

Obesity is an excessive increase in body fat mass and triggers chronic inflammation which causes increased fat accumulation in the visceral fat tissue. The aim of this study was to analyze serum zinc (Zn), Zn-alpha 2 glycoprotein (ZAG), peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) levels in morbidly obese patients before and after laparoscopic sleeve gastrectomy (LSG) and determine the association between alteration in body mass index (BMI), the % Excess Weight Loss (% EWL) and the biochemical parameters. Thirty healthy individuals as a control group and 30 morbidly obese patients who had undergone LSG were enrolled in this study. Routine anthropometric and laboratory biochemical parameters in venous blood samples of groups at baseline and 1 and 12 months after LSG were recorded. Significant weight loss was achieved at 1 and 12 months after LSG. At baseline serum ZAG and PPAR-γ levels were lower, while NF-кB levels were higher in morbidly obese patients compared with the control group. Serum ZAG and PPAR-γ levels increased while NF-кB levels decreased 1 month and 12 months after LSG. Decreased %EWL was negatively correlated with changes in NF-кB, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting plasma glucose and insulin at 12 months after LSG in morbidly obese patients. However, %EWL was positively correlated with changes in ZAG. Obesity was associated with down-regulated serum ZAG and PPAR-γ levels while up-regulated serum NF-кB. Our findings suggest that LSG ameliorates upregulating PPAR-γ expression, thereby inhibiting NF-κB-mediated inflammation by weight loss.

Аналіз взаємозв`язку композиційного складу тіла та рівня функціональної підготовленості футболістів

The compositional content of the body of athletes is one of the factors that can affect the effectiveness of sports activity, being an important component of the training process of football players. In turn, the composition of the body depends on the orientation, intensity and volume of training loads. Physical activity and exercise are known to lead to a decrease in body fat and an increase in lean body mass. The purpose of the study was to determine the significance of body composition for functional readiness of football players. Material and methods. The research involved 81 football players (Ukrainian Premier League), aged 20-30 years. During the research, the following methods were used: chronometry, ergometry, spirometry, gas analysis, heart rate monitoring, anthropometry and impedance measurement, biochemical research methods, and mathematical statistics methods. Results and discussion. As a result of the study, we established the influence of the body composition, in particular the percentage of body fat, on the level of functional readiness of football players. The probable correlations between the values of the level of functional readiness and indicators of the composition of the body were revealed. We found probable correlation between lean body mass and absolute power (r = 0.90; p ≤ 0.05), lean mass and VO2max (r = 0.44; p ≤ 0.05). A probable correlation between the percentage of fat and specific power (r = - 0.45; p ≤ 0.05), the percentage of fat and speed (r = - 0.50; p ≤ .05) was also revealed. An increase in body fat mass can negatively affect the specific power, speed and aerobic capabilities of athletes; it manifests itself in a decrease in the VO2max, speed and power of football players with an increase in body weight due to the fat component. Conclusion. The highest values of maximum power and VO2max were achieved by football players with adipose tissue content in the range from 9.0 to 16.0%. An increase in the level of functional readiness of football players is possible by optimizing the compositional composition of the body of athletes, namely, the percentage of body fat

Oxidative stress resulting from the removal of endogenous catalase induces obesity by promoting hyperplasia and hypertrophy of white adipocytes

Obesity is regarded as an abnormal expansion and excessive accumulation of fat mass in white adipose tissue. The involvement of oxidative stress in the development of obesity is still unclear. Although mainly present in peroxisomes, catalase scavenges intracellular H2O2 at toxic levels. Therefore, we used catalase-knockout (CKO) mice to elucidate the involvement of excessive H2O2 in the development of obesity. CKO mice with C57BL/6J background gained more weight with higher body fat mass with age than age-matched wild-type (WT) mice fed with either chow or high-fat diets. This phenomenon was attenuated by concomitant treatment with the antioxidants, melatonin or N-acetyl cysteine. Moreover, CKO mouse embryonic fibroblasts (MEFs) appeared to differentiate to adipocytes more easily than WT MEFs, showing increased H2O2 concentrations. Using 3T3-L1-derived adipocytes transfected with catalase-small interfering RNA, we confirmed that a more prominent lipogenesis occurred in catalase-deficient cells than in WT cells. Catalase-deficient adipocytes presented increased nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression but decreased adenosine monophosphate-activated protein kinase (AMPK) expression. Treatment with a NOX4 inhibitor or AMPK activator rescued the propensity for obesity of CKO mice. These findings suggest that excessive H2O2 and related oxidative stress increase body fat mass via both adipogenesis and lipogenesis. Manipulating NOX4 and AMPK in white adipocytes may be a therapeutic tool against obesity augmented by oxidative stress.

Increased body fat mass reduces the association between fructosamine and glycated hemoglobin in obese type2 diabetes patients.

Obesity is increasing in patients with type 2 diabetes. A possible reduced association between fructosamine and glycated hemoglobin (HbA1c) in obese individuals has been previously discussed, but this has never been specifically evaluated in type 2 diabetes, and the potential influence of body fat mass and fat distribution has never been studied. We studied 112 type 2 diabetes patients with assessment of fat mass, liver fat and fat distribution. Patients with body mass index (BMI) above the median (34.9 kg/m2), versus BMI below the median, had a correlation coefficient between fructosamine and HbA1c significantly reduced (r = 0.358 vs r = 0.765). In the whole population, fructosamine was correlated negatively with BMI and fat mass. In multivariate analysis, fructosamine was associated with HbA1c (positively) and fat mass (negatively), but not with BMI, liver fat or fat distribution. The association between fructosamine and HbA1c is significantly reduced in the most obese type 2 diabetes patients, and this is mostly driven by increased fat mass.

Anthropometric and Skin Fold Thickness Measurements of Newborns of Gestational Glucose Intolerant Mothers: Does it Indicate Disproportionate Fetal Growth?

Studies have shown that gestational diabetes mellitus (GDM) causes disproportionate growth and increased adiposity in their newborns; however, the effect of gestational glucose intolerance (GGI), i.e., 2h plasma glucose (PG) between 120 and 139mg/dl in pregnancy on their newborns growth and adiposity is not well established. The objective of the present study is to evaluate the effect of GGI in pregnancy on anthropometry and adiposity of their newborns at birth in urban South Indian population. An observational study was conducted on 119 urban South Indian pregnant women and their newborns. PG levels 2h after ingestion of 75g glucose load were determined between 24 and 28weeks of gestation, and depending on their PG levels, these women were categorized into three different groups, (a) normal glucose tolerance (NGT)-2h PG < 120mg/dl, (b) GGI-2h PG between 120 and 139mg/dl and (c) GDM-2h PG > or = 140mg/dl. GDM mothers were treated with insulin and MNT advised. GGI mothers were advised MNT. These women were followed up till delivery. After delivery, their newborn's anthropometry like weight, length, head circumference (HC), chest circumference (CC), mid-arm circumference, abdominal circumference, bisacromial diameter and subscapular and triceps skin fold thicknesses (SFT) was measured within 72h of birth. Effect of GGI in pregnancy on newborn's anthropometry and SFT was analyzed and studied in comparison with newborns of other two categories. Further, the newborns were stratified into four groups according to their birth weight and newborns of GGI category were compared with newborns of other two categories of same weight. The triceps and subscapular skin fold thicknesses which are direct measurements of adiposity were significantly higher in newborns of GGI mothers compared to newborns of GDM and NGT mothers. GGI category newborns showed increased adiposity even when they were compared with newborns of GDM and NGT category of same weight. Also measurements which are likely to increase due to increased adiposity like bisacromial diameter, abdominal circumference, mid-arm circumference were significantly higher in GGI category newborns. On the other hand, measurements which indicate skeletal growth like length, HC, CC were similar in all three category newborns. This confirmed disproportionate growth and increased adiposity in newborns of GGI mothers.It should be noted here that the GDM mothers were on MNT andtreated with insulin, the dose of insulin was adjusted so as to mimick FastingPG and PostPrandial PG levels of NGT mothers. Gestational glucose intolerance during pregnancy does cause disproportionate growth (increased fat body mass but not skeletal mass) and increased adiposity in their newborns. This emphasizes the need for strict glycemic control (2h of PG level after 75 grams glucose load to < 120mg/dl and PPPG levels to < 120mg/dl) during pregnancy. Larger multicentered studies are recommended to confirm this association.

Muscle mass is the main somatic growth indicator associated with increasing blood pressure with age in children and adolescents.

Studies have shown that lean mass must be an important determinant of blood pressure value in children and adolescents. The absence of adjustment for the collinearity between lean and fat mass (FM), restricted age span, and lack of separate analysis by sex leave a gap in the literature. This study determined direct and indirect effects of the somatic growth indicators linked to the association between age and systolic blood pressure (SBP) in boys and girls. This is a cross-sectional study comprising 1,510 participants (6-18years). Path analysis was used to test a model in which the association between age and SBP would have a direct and independent component, but also indirect mediating paths through muscle mass (MM), FM, and height. There was no significant association between age and SBP (unstandardized β±SE) for both girls (0.072±0.236, P=.761) and boys (0.238±0.264, P=.368). Height was not a mediator for the association between age and SBP in both girls (-0.291±0.156, P=.062) and boys (-0.015±0.187, P=.935). Mediating effect of MM was significant for both girls (0.909±0.137, P<.001) and boys (1.341±0.161, P<.001), whereas mediating path through FM was significant only for boys (0.069±0.023, P=.003). In conclusion, muscle mass was the strongest somatic growth indicator associated with the blood pressure value in children and adolescents. Further increase in body fat mass may affect systolic blood pressure more in boys than in girls.

Causal Pathways from Body Components and Regional Fat to Extensive Metabolic Phenotypes: A Mendelian Randomization Study.

The aim of this study was to explore the causal effects and pathways from body components to extensive metabolic phenotypes. Summarized data including 24 metabolic phenotypes from 10 consortiums were used to perform univariate, multivariable, and bidirectional Mendelian randomization analysis based on the network design. For metabolically related biomarkers, a 1-SD increase in body fat mass (BFM) was robustly associated with increased fasting insulin, systolic blood pressure, diastolic blood pressure, and urate and decreased high-density lipoprotein cholesterol levels. For metabolically related diseases, the odds ratios and 95% CIs of a 1-SD increase in BFM were 1.76 (1.37 to 2.25) for type 2 diabetes mellitus (T2DM), 1.11 (1.09 to 1.13) for hypertension, 1.40 (1.25 to 1.57) for coronary artery disease, 1.41 (1.25 to 1.59) for myocardial infarction, 1.25 (1.12 to 1.40) for ischemic stroke, and 1.62 (1.02 to 2.57) for gout. The effects of body fat on diseases were mediated by extensive intermediate biomarkers, including blood pressure, lipids, glycemic traits, and urate. Regional fats had a similar effect with body fat in both absolute and relative scales, whereas fat-free components increased only the risk of T2DM 1.73 (1.11 to 2.68) and chronic kidney disease 1.51 (1.11 to 2.06). Several potential pathways were found and confirmed the tremendous benefits of fat-lowering measures, including lowering of various regional fats. Future policies or interventions should focus more on the role of body fat.

YNCRG Inhibited Metabolic Syndrome Through Appetite Suppression and Improved Lipid Metabolism in Metabolic Syndrome Model Rats

Increased body fat mass can lead to lifestyle diseases such as hypertension, diabetes, and hyperlipidemia. Metabolic syndrome is a cluster of conditions that increases the onset of multiple diseases, such as cardiovascular diseases, stroke, and type 2 diabetes, which are closely related to lipid metabolism; therefore, new prevention approaches and treatments are needed. Our study investigated the effects and mechanism of YNCRG on anti-obesity in metabolic syndrome model SHR.Cg-Leprcp/NDmcr (SHRCP) rats. Eight-week-old male SHRCP rats were administered YNCRG or water by gavage for eight weeks and sacrificed. The tissues were immediately dissected for future experiments. We also used WKY rats as a rodent model. YNCRG induced reductions in food intake, body weight, and body fat mass in SHRCP rats. We also analyzed the mechanism of food intake regulation in the hypothalamus. Expression of POMC was significantly increased in the YNCRG group. However, JAK2 showed no change between the two groups. Phosphorylation levels of Akt (Ser473) and FoxO1 were significantly increased in the YNCRG group. Moreover, mTOR was significantly phosphorylated by YNCRG treatment. These results suggest that YNCRG can induce appetite suppression through the mTOR-Akt-FoxO1-POMC signaling pathway. YNCRG also induced a reduction in body fat mass. In adipose tissue, phosphorylation of AMPK was significantly increased in the YNCRG group. Also, LKB1 and PKA (upstream factors of AMPK), and ACC and HSL (downstream factors of AMPK) were significantly phosphorylated with the YNCRG treatment. Our results indicate that YNCRG can treat MetS by decreasing body fat mass of SHRCP rats through appetite suppression and improvement of lipid metabolism.

P0821OBESITY, FAT TISSUE, CELL MEMBRANE INTEGRITY PARAMETERS AND ARTERIAL STIFFNESS IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Arterial stiffness, altered body composition (increased body fat mass and decreased soft lean mass) and cell membrane integrity (Phase Angle) are acknowledged risk factors for adverse outcomes after kidney transplantation related to cardiovascular diseases. Phase angle is a linear method of measuring the relationship between electric resistance and reactance. Taking the arc tangent value of the ratio of reactance versus electric resistance provides us with the phase angle value. Lower phase angles appear to be consistent with low reactance and equals either cell death or a breakdown in the selective permeability of the cell membrane. The aim of the study was the assessment of the relationship between arterial stiffness and fat tissue parameters, cell membrane integrity marker in renal transplants recipients (RTRs). Method 344 stable RTRs with the mean age 52.7 years, (62.5% M) transplanted between 1994 and 2018 were randomly enrolled to the study. The following parameters of arterial stiffness were measured: brachial-ankle and carotid-femoral pulse wave velocities (baPWV left and right, cfPWV). The obesity and fat tissue (body mass index (BMI), waist to hip ratio (WHR), body fat mass (BFM), fat free mass (FFM), percent fat of the body (PBF), trunk segmental fat analysis (TSFA) and visceral fat area (VFA)) parameters and cell membrane integrity phase angle (PhA) were assessed with InBody 170. Results The median time of dialysis and after kidney transplantation was 58.5 and 78 months respectively. The obesity according to BMI, WHR and VFA was diagnosed in 49.7%, 45% and 44.5% of patients, respectively. The median value of BFM, FFM, VFA, TSFA, PhA and the mean value of PBF were 19.3kg, 55kg, 93.2cm2, 24.9 kg, 4.9 and 27.3%, respectively. We found significant positive correlations between WHR, VFA and baPWV right, baPWV left and cfPWV. PhA correlated with arterial stiffness in univariate (r=-0.34) and multivariate analysis (R=-0.23), negatively (p&amp;lt;0.05). Conclusion 1. Obesity, visceral fat tissue, cell membrane integrity marker influence on arterial stiffness. 2. The analysis of magnitude of obesity, body fat tissue and cell membrane integrity parameters can be used as an additional cardiovascular risk factor in RTRs. 3. The cell membrane integrity impairment correlated with arterial stiffness.

2’-fucosyllactose (2’-FL) Supplementation Improves Gut Barrier Function and Lipid Metabolism in HF-fed Mice

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).

Effects of abomasal infusion of essential fatty acids together with conjugated linoleic acid in late and early lactation on performance, milk and body composition, and plasma metabolites in dairy cows

Rations including high amounts of corn silage are currently very common in dairy production. Diets with corn silage as forage source result in a low supply of essential fatty acids, such as α-linolenic acid, and may lead to low conjugated linoleic acid (CLA) production. The present study investigated the effects of abomasal infusion of essential fatty acids, especially α-linolenic acid, and CLA in dairy cows fed a corn silage-based diet on performance, milk composition, including fatty acid (FA) pattern, and lipid metabolism from late to early lactation. Rumen-cannulated Holstein cows (n = 40) were studied from wk 9 antepartum to wk 9 postpartum and dried off 6 wk before calving. The cows were assigned to 1 of 4 treatment groups. Cows were abomasally supplemented with coconut oil (CTRL, 76 g/d), linseed and safflower oil (EFA, 78 and 4 g/d; linseed/safflower oil ratio = 19.5:1; n-6/n-3 FA ratio = 1:3), Lutalin (CLA, 38 g/d; BASF SE, Ludwigshafen, Germany; isomers cis-9,trans-11 and trans-10,cis-12 each 10 g/d) or EFA+CLA. Milk composition was analyzed weekly, and blood samples were taken several times before and after parturition to determine plasma concentrations of metabolites related to lipid metabolism. Liver samples were obtained by biopsy on d 63 and 21 antepartum and on d 1, 28, and 63 postpartum to measure triglyceride concentration. Body composition was determined after slaughter. Supplementation of CLA reduced milk fat concentration, increased body fat mass, and improved energy balance (EB) in late and early lactation, but EB was lowest during late lactation in the EFA group. Cows with CLA treatment alone showed an elevated milk citrate concentration in early lactation, whereas EFA+CLA did not reveal higher milk citrate but did have increased acetone. Milk protein was increased in late lactation but was decreased in wk 1 postpartum in CLA and EFA+CLA. Milk urea was reduced by CLA treatment during the whole period. After calving, the increase of nonesterified fatty acids in plasma was less in CLA groups; liver triglycerides were raised lowest at d 28 in CLA groups. Our data confirm an improved metabolic status with CLA but not with exclusive EFA supplementation during early lactation. Increased milk citrate concentration in CLA cows points to reduced de novo FA synthesis in the mammary gland, but milk citrate was less affected in EFA+CLA cows, indicating that EFA supplementation may influence changes in mammary gland FA metabolism achieved by CLA.

0699 Effect Of Kidney Transplantation On Sleep Apnea Severity: A Prospective Controlled Polysomnographic Study

Abstract Introduction Renal failure-associated fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end-stage kidney disease (ESKD). Kidney transplantation has been shown to restore a normal renal function but its effect on SA remains unclear. In this prospective study, we hypothesized that improvement of kidney function and hydration status after kidney transplantation (Tx) may result in an improvement of SA severity. Methods A total of 196 patients on kidney transplant waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the Apnea-Hypopnea Index (AHI) and underwent bioimpedance to assess body composition. Polysomnography and bioimpedance were repeated 6 months after kidney transplant. Patients still on the waiting list after 6 months underwent same investigations as a control group. Results Of 88 participants (44.9%) with SA (AHI ≥15/h) at baseline, 42 patients were reassessed 6 months post-Tx and were compared to 27 control patients remaining on the waiting list after 6 months. There was a significant, although partial, post-Tx improvement in SA severity as measured by the AHI (from 44.2±24.3/h to 34.7±20.9/h, p=0.02), with a concomitant reduction in body water (from 54.9% to 51.6%, p=0.003), suggesting a causal implication of fluid overload. A post-Tx increase in body fat mass (from 26% to 30%, p=0.003) may have blunted the beneficial impact of kidney Tx on SA. These parameters remained unchanged in the control group. Conclusion SA is a frequent condition in ESKD patients. Kidney transplantation is associated with a reduction of fluid overload but an increase in fat mass, yielding only a partial improvement in SA severity. These results suggest that SA should be systematically assessed before and after kidney Tx Support Swiss Kidney Foundation, the Pulmonary League and the Organ Transplant Foundation of Lausanne

Obesity, Fat Tissue Parameters, and Arterial Stiffness in Renal Transplant Recipients

ObjectiveArterial stiffness and altered body composition (increased body fat mass [BFM] and decreased lean body mass) are acknowledged risk factors for adverse outcomes after kidney transplantation related to cardiovascular diseases. The aim of the study was the assessment of the relationship between arterial stiffness and fat tissue parameters in renal transplants recipients (RTrs). MethodsA group of 344 RTrs with stable disease and a mean age of 52.7 years (62.5% men) who underwent transplantation between 1994 and 2018 were randomly enrolled in the study. The following parameters of arterial stiffness were measured: brachial-ankle and carotid-femoral pulse waves velocities (baPWVs left and right, cfPWVs). The obesity and fat tissue (body mass index [BMI], waist-to-hip ratio [WHR], BFM, fat free mass [FFM], percent body fat [PBF], trunk segmental fat analysis [TSFA], and visceral fat area [VFA]) parameters were assessed with InBody 170. ResultsThe median time of dialysis and after kidney transplantation was 58.5 and 78 months, respectively. Obesity according BMI, WHR, and VFA was diagnosed in 49.7%, 45.0%, and 44.5% of patients, respectively. The median value of BFM, FFM, VFA, and TSFA and the mean value of PBF were 19.3 kg, 55 kg, 93.2 cm2, 24.9 kg, and 27.3%, respectively. We found significant positive correlations among WHR, VFA, baPWV right, baPWV left, and cfPWV. ConclusionsObesity and visceral fat tissue influence on arterial stiffness. The analysis of magnitude of obesity and body fat tissue parameters can be used as an additional cardiovascular risk factor in RTrs.

Dietary Fat and Sugar Differentially Affect β-Adrenergic Stimulation of Cardiac ERK and AKT Pathways in C57BL/6 Male Mice Subjected to High-Calorie Feeding

High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways. Male C57BL/6 mice (9 wk old; n=20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only. Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P<0.001), induced glucose intolerance (P<0.001), and increased insulin concentrations >1.5-fold (P<0.05), thereby enhancing basal and ISO-stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+25-63%; P<0.05). Compared with HFD, the high-sugar diets potentiated ISO-mediated stimulation of the glucose-sensitive kinases PYK2 (>47%; P<0.05 for HCD and HSD) and ERK (>34%; P<0.05 for WD, HCD, and HSD), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (>64%; P<0.05 for WD, HCD, and HSD). Dietary fat and sugar affect cardiac growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological cardiac remodeling.