Fat Mass Accumulation Research Articles

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.

Relationship Of Physical Activity To Total Fat Mass Of Lecturers And Employees Bengkulu University

Insufficient physical activity and accumulation of body fat mass are risk factors for chronic disease. Physical activity is needed to prevent the risk of chronic disease due to body fat accumulation. This research is an observational analytic study with a cross sectional design. A sample of 52 people was taken by consecutive sampling method including lecturers and employees aged 30-60 years at the Faculty of Teacher Training and Education, University of Bengkulu (FKIP UNIB). Physical activity was analyzed using the Physical Activity Level (PAL) questionnaire, total fat mass was assessed by means of Bioelectrical Impedance Analysis (BIA). Data distribution analysis was tested using the Kolmogorov-Smirnov test. Analysis of the relationship between two categorical variables with the Chi-square test, the Kruskal-Wallis and Mann Whitney test. The correlation analysis between the two variables was analyzed using the Gamma correlation test. The results of this study indicate that there is a significant relationship between physical activity and total fat mass (p = 0.031, r = 0.428) after being analyzed with Gamma correlation. It can be concluded that physical activity has a relationship with total fat mass.

Serum nesfatin in overweight and obese children

BACKGROUND: Obesity is one of the most common children diseases. In present time it is being actively studied the natural hormones role in the pathogenesis of obesity.
 AIMS: To determine the relationship between serum nesfatin level with impaired lipid metabolism in school age children with overweight and obesity.
 MATERIALS AND METHODS: The study included children with overweight and obesity (case) and healthy children with normal body mass (control) aged 9 to 15 years. All children were determined by concentration in cholesterol blood and its factions, apoA-1, apoB. Enzyme-linked immunosorbent assay (Bio Human Nesfatin Enzyme Immunoassay Kit).
 RESULTS: Groups of patients with overweight and obesity (n = 53) and healthy children (n = 31) were comparable by age and sex. In obese children, a significant decrease in the level of nesfatin-1 was revealed compared with the group with normal body weight. In cases of children obesity there is a marked decrease in the concentration of nesfatin-1 in serum, especially expressed in the dyslipidemia presence. The nesfatin-1 level are negatively correlated to BMI and body fat content.
 CONCLUSIONS: The obtained data suggest that along with the known key role of nesfatin in the regulation of eating behavior and appetite, it also affects anthropometric indicators, primarily associated with the accumulation of excess fat mass. Based on the data obtained, nesfatin-1 should be considered as a possible marker for the development of obesity in children.

Infant body composition relationship to maternal adipokines and fat mass: the PONCH study.

Infant adiposity is linked to both high maternal fat mass (FM) and excessive gestational FM gain, whereas the association with maternal adipokines is less clear. The aim was to determine how levels of maternal leptin, the soluble leptin receptor (sOB-R), adiponectin, and FM during pregnancy were linked to infant FM in normal-weight (NW) women and women with obesity (OB). Body composition and serum levels of leptin, adiponectin, and sOB-R were determined three times during pregnancy in 80 NW and 46 OB women. For infants, body composition was measured at 1 and 12 weeks of age. Maternal leptin and sOB-R levels increased during pregnancy. For NW women, infant FM at 1 week was inversely associated with changes in maternal leptin and at 12 weeks inversely associated with absolute maternal sOB-R levels throughout pregnancy, as well as changes in sOB-R levels in early pregnancy. For OB women, infant FM at both 1 and 12 weeks were best explained by maternal FM. Leptin and sOB-R, thought to regulate leptin bioavailability, are associated with fat accumulation in infants born to NW women. In OB women, maternal FM in early pregnancy is more important than leptin in determining infant fat accumulation. In normal-weight women, the regulation of maternal leptin bioavailability during pregnancy has a role in infant fat mass accumulation. In women with obesity, however, pre-pregnancy maternal fat mass seems more important for infant fat mass. This is the first study of maternal adipokines and fat mass including longitudinal measurements in both mothers and their children. Understanding the relationship between maternal factors and infant fat mass is of great importance as obesity is programmed over the generations, and it is important to learn what regulates this programming.

Leptin signalling on arcuate NPY neurones controls adiposity independent of energy balance or diet composition.

Central action of the adipocyte hormone leptin via the neuropeptide Y (NPY) system is considered critical for energy homeostatic control. However, the precise mechanisms for this control are still not clear. To specifically investigate how leptin signalling on the NPY neurone contributes to the control of energy homeostasis, we generated an inducible adult-onset NPY neurone-specific leptin receptor (Lepr) knockout model and performed a comprehensive metabolic phenotyping study. Here, we show that the NPY neurone subpopulation that is directly responsive to leptin is not required for the inhibition of fasting-induced hyperphagia by leptin, although it is essential for the regulation of adiposity independent of changes in energy balance or diet composition. Furthermore, under obesogenic conditions such as a high-fat diet, a lack of Lepr signalling on NPY neurones results in significant increases in food intake and concomitant reductions in energy expenditure, leading to accelerated accumulation of fat mass. Collectively, these findings support the notion that Lepr-expressing NPY neurones act as the key relay point where peripheral adipose storage information is sensed, and corresponding responses are initiated to protect adipose reserves.

COVID-19-Related Home Confinement in Adults: Weight Gain Risks and Opportunities.

As the global COVID-19 pandemic unfolds, over 90% of U.S. adult residents are confined to their homes, with restaurants, shops, schools, and workplaces shut down to prevent disease spread. While it is a priority to mitigate the immediate impact, one area of great concern is the long-term effects of this pandemic on weight management in adults. As evident from previous research, small changes in body weight in relatively short time periods can become permanent and lead to substantial weight gain over time(1). Considering that the current situation could last a total of several months, this extended home confinement could exacerbate the problem of obesity in adults by substantially contributing to or exceeding annual weight gain.

1868-P: Implementation of Dietary Methionine Restriction Using Casein after Selective, Oxidative Deletion of Methionine

Restriction of methionine in rodent diets increases energy expenditure, limits weight gain, improves insulin sensitivity, and reduces hepatic and circulating lipids. Dietary methionine restriction (MR) is implemented using diets formulated from elemental amino acids (AA) that reduce methionine content to restricted levels of ∼0.17%. However, translational implementation of dietary MR with elemental AA-based diets is confounded by poor palatability. To solve this problem and restrict methionine using intact proteins, casein was subjected to mild oxidation to selectively reduce methionine. Diets were then formulated using oxidized casein, adding back methionine to produce a final concentration of 0.17%. The biological efficacy of dietary MR using the oxidized casein diet was compared to the standard elemental MR diet. Thirty-two, 5-week old male C57BL/6J mice were divided into two groups of 16, with one group receiving the Elemental Control (El Con) diet and the other receiving the Casein Control (Cas Con) diet for 10 days. Thereafter, 8 mice continued on the El Con diet and 8 mice were switched to the Elemental MR (El MR) diet. In similar fashion, 8 mice continued on the Cas Con diet and 8 mice were switched to the Oxidized Casein (Ox Cas) MR diet. Over the subsequent 8 weeks, the behavioral, metabolic, and endocrine responses to the 4 diets were assessed to evaluate the relative efficacy of the 2 approaches to restricting dietary methionine. The El MR diet produced the expected reductions in body weight, fat mass accumulation, fasting insulin, and hepatic and circulating triglycerides, while increasing energy expenditure, serum FGF-21 levels, and weight-specific food consumption. The Ox Cas MR diet produced increases and decreases in each of these variables that paralleled the effects of the El MR diet. Collectively, these findings demonstrate that dietary MR can be effectively implemented using casein after selective oxidative reduction of methionine. Disclosure H. Fang: None. K.P. Stone: None. L. Forney: None. L.C. Sims: None. T.W. Gettys: None. Funding Pennington Foundation

1950-P: Fat Mass Affects Metabolic Response to Erythropoietin in Mice

Erythropoietin (EPO) is required for erythrocyte production. However, EPO receptor (EpoR) expression extends beyond erythroid tissue. To assess EPO activity on glucose homeostasis and fat mass accumulation, wild type (WT, C57BL/6) mice, ΔEpoRE mice with EpoR restricted to hematopoietic tissue and ΔEpoRWAT mice with targeted EpoR deletion in fat tissue were fed a high fat diet (HFD, 60% kCal fat) and treated with EPO (3000U/kg 3X per week) or saline for 3 weeks at age 3, 4, and 6 months. EPO increased hematocrit in all mice and improved glucose tolerance when fat mass was less than 35% which included all female mice. In male WT mice EPO improved glucose tolerance and reduced fat mass which at 6 months was 40% on HFD and below 35% with HFD/EPO treatment. In female mice, estrogen interferes with EPO fat mass regulation. EPO treatment did not affect fat mass in ΔEpoRE mice, indicating that EPO regulation of fat mass is a non-hematopoietic response. EPO improved glucose tolerance in female and only age 3 month male ΔEpoRE mice when fat mass was less than 35%. In male ΔEpoRWAT mice, EPO minimally reduced fat mass indicating that EPO fat mass regulation in males is largely a direct fat tissue response. EPO treatment improved glucose tolerance in male ΔEpoRWAT mice when fat mass was below 35% but not at 6 months when fat mass exceeded 40%. These data demonstrate that EPO improved glucose tolerance when fat mass was below 35%, that the sex-dimorphic EPO regulation of fat mass is primarily mediated by EpoR in fat, and that EPO activity in glucose metabolism and fat mass is differentially regulated and does not follow EPO stimulated erythropoiesis. Disclosure H. Rogers: None. C.T. Noguchi: None. Funding National Institutes of Health

578-P: A Loss-of-Function Mutation of NRG4 Contributes to the Pathogenesis of NAFLD and Insulin Resistance

Neuregulin 4 (Nrg4), as an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication which elicits beneficial metabolic effects in NAFLD. We identified a mutation of NRG4 by whole exome sequencing in 151 severe obese subjects and exome array in a community-based population of 2388 subjects. Nrg4 R44H mutation carriers have increased visceral fat area, abnormal liver function and hyperlipidemia. Then we hypothesized that the mutation would affect the function of Nrg4 and accelerated the development of NAFLD. Compared with Nrg4 WT mice, Nrg4 R44H mice gained more weight, accompanied by significantly increased fat mass and lipid accumulation in the liver upon HFD feeding. In vitro, we found that Nrg4 WT activated ErbB4 and stimulated the STAT5 signaling pathway and decreased transcriptional activation of srebp1c. As we hypothesized, the primary hepatocytes treated with Nrg4 R44H purified protein didn’t showed the same activation of cell signaling as Nrg4 WT. In order to reveal the potential mechanisms of loss-of-function of Nrg4 R44H, we performed surface plasmon resonance (SPR) experiments to test the binding affinity of purified Nrg4 and ErbB4 proteins. The SPR results showed Nrg4 WT bind to ErbB4 with an affinity of 2.20uM, while Nrg4 R44H showed no binding. Taken together, these results suggested Nrg4 WT prevented HFD-induced NAFLD and alleviated insulin resistance, and demonstrated Nrg4 R44H lost its ability to bind to the receptor ErbB4, thus losing its physiological function. Disclosure C. Hu: None. Y. Li: None.

A systematic review of precision nutrition and Mediterranean Diet: A personalized nutrition approaches for prevention and management of obesity related disorders.

The Obesity is related to type 2 diabetes, and diseases with metabolic syndrome characteristics such as dyslipidemia, hypertension and cardiovascular illness. The nutrition is the most important environmental factor that modulates the phenotype type of obesity. The impacts of nutrients might modulate the gene expression. The recent studies have focused on the relationship between obesity in terms of gene-environment interactions. There is a relationship between genetic indicators, fat mass accumulation, body composition and Mediterranean diet. The evaluation of nutrition treatment or interventions together with the genetic state; provides to manage or prevent the development of chronic diseases. As a result of nutrigenetic studies; specific nutrition factors in Mediterranean Diet have positive effects on gene expressions related to obesity. In the future, the rapidly-developing nutrition science and the optimal nutrition model special for individuals might play an important role in terms of health development and healing. This metanalysis aimed to explain the current status and relationship between metabolic syndrome indicators that are related to obesity and the gene-nutrient interactions within the Mediterranean Diet.

Obesogenic diet-associated C-reactive protein predicts reduced central dopamine and corticostriatal functional connectivity in female rhesus monkeys

Alterations in dopamine (DA) signaling and reductions in functional connectivity (FC; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including C-reactive protein. Peripheral and central inflammatory cytokines that have been shown to disrupt DA signaling and corticostriatal FC are associated with C-reactive protein, an acute phase reactant that is used translationally as a marker of systemic inflammation. One factor that can significantly increase systemic inflammation to produce neuroadaptations in reward pathways is a diet that results in fat mass accumulation (e.g. obesogenic diet). The current study in female rhesus monkeys maintained in a standard laboratory chow (n = 18) or on obesogenic diet (n = 16) for 12-months tested the hypothesis that an obesogenic diet would alter central DA and homovanillic acid (HVA) concentrations, and be associated with increased CRP concentrations and decreased FC between corticostriatal regions at 12-months following dietary intervention. We specifically assessed FC between the nucleus accumbens (NAcc) and two sub-regions of the prefrontal cortex (PFC) previously associated with CRP concentrations, the ventromedial PFC (vmPFC) and the orbitofrontal cortex (OFC), which are also involved in emotional and motivational salience assessment, and in goal-directed behavior, impulse control and the salience/value of food, respectively. Results showed that CSF DA concentrations were decreased (p = 0.002), HVA:DA ratios were increased (p = 0.016), and body mass index was increased (p = 0.047) over the 12-months of consuming an obesogenic diet. At 12-months, females maintained in the obesogenic diet exhibited higher CRP concentrations than females consuming chow-only (p = 0.008). Linear regression analyses revealed significant CRP by dietary condition interactions on DA concentrations (β = −5.10; p = 0.017) and HVA:DA ratios (β = 5.14; p = 0.029). Higher CRP concentrations were associated with lower CSF DA concentrations (r = −0.69; p = 0.004) and greater HVA:DA ratios only in females maintained in the obesogenic dietary condition (r = 0.58; p = 0.024). Resting-state magnetic resonance neuroimaging (rs-fMRI) in a subset of females from each diet condition (n = 8) at 12-months showed that higher CRP concentrations were associated decreased FC between the NAcc and subregions of the prefrontal cortex (PFC; p’s < 0.05). Decreased FC between the NAcc and PFC subregions were also associated with lower concentrations of DA and greater HVA:DA ratios (p’s < 0.05). Overall, these data suggest that increased inflammatory signaling driving heightened CRP levels may mediate the adverse consequences of obesogenic diets on DA neurochemistry and corticostriatal connectivity.

Adiposity is inversely associated with strength in older adults with type 2 diabetes mellitus.

Several biological mechanisms describing the pathway to mobility disability and functional decline in older adults with type 2 diabetes mellitus (T2DM) have been postulated, including skeletal muscle atrophy and the concurrent accumulation of fat mass. Therefore, we explored the association between adiposity, muscle strength and physical performance in community-dwelling older adults with T2DM. Adiposity was measured by waist circumference (WC) or body fat percentage (BF %) derived from dual-energy X-ray absorptiometry (DXA). The Short Physical Performance Battery (SPPB) and gait speed were used to evaluate lower extremity physical function. Muscle strength was assessed using hand-grip strength (HGS) or chair stands. Multiple regression analysis was used to examine the association between measures of adiposity, SPPB score, gait speed, HGS and chair stands adjusted for age, gender and total appendicular skeletal muscle (ASM). A total of n = 87 participants (71.2 ± 8.2years; BMI 29.5 ± 5.8kg/m2; BF % 37.8 ± 7.3%) were included in this cross-sectional analysis. Pearson's correlation coefficients revealed that BF% was negatively associated with hand-grip strength (r = -0.430; P < 0.001) and total ASM (r = -0.223; P = 0.03), but positively associated with increased time to compete chair stands (r = 0.366; P < 0.001). After adjusting for age, gender and total ASM, WC and BF% were inversely associated with HGS (WC: β = -0.385; P = 0.001; BF% β = -0.487; P < 0.001). Similarly, in the adjusted model, both WC and BF% were positively associated with increased time to complete chair stands (WC: β = 0.479; P < 0.001; BF% β = 0.415; P = 0.002). Adiposity, independent of the criteria used, was inversely associated with muscle strength, suggesting that adiposity negatively influences muscle quality in older adults with T2DM. Screening for poor muscle strength and quality has the potential to facilitate early exercise and dietary interventions aimed at preserving muscle function in older adults with T2DM.

Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions

Melinjo seed extract (MSE) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin C, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSE supplementation increases the adiponectin (APN) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet- or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/total APN in relation to the genes regulating APN multimerization, including DsbA-L. Furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. In addition, the administration of MSE to HFD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW APN in serum and the mRNA levels of ADIPOQ and DsbA-L in adipose tissue. The present study suggests that MSE may exert beneficial effects via APN multimerization in relation to the induction of DsbA-L under both physiological and obese conditions.

Associations of Weight-Adjusted Body Fat and Fat Distribution with Bone Mineral Density in Chinese Children Aged 6-10 Years.

Although obesity is considered osteoprotective, the effects of body fat and fat distribution on bone tissue after adjusting for the effects of body weight remain uncertain. This study evaluated the relationships between fat mass, fat distribution, and bone mineral status beyond its weight-bearing effect. We recruited 466 children aged 6–10 years in China. Dual-energy X-ray absorptiometry was used to determine the bone mineral density (BMD) and bone mineral content (BMC) in the total body and total body less head (TBLH), as well as the fat mass (FM) and percentage fat mass (%FM) of the total and segmental body. Weight-adjusted measures of FM and %FM were derived using the residual method. After adjusting for the effects of covariates, we observed statistically significant, dose-dependent negative relationships between the TBLH·BMD/BMC and various weight-adjusted measures of body fat (p for trend: <0.001–0.038). For each standard deviation increment in the weight-adjusted total body, TBLH, trunk and limbs, the size-adjusted BMC decreased approximately 9.44, 9.28, 8.13, and 6.65 g in boys, respectively, and by approximately 13.74, 13.71, 7.84, and 12.95 g in girls, respectively. Significant inverse associations between FM accumulation in the total body and most body parts with the BMD/BMC were observed in both boys and girls after adjusting for weight and potential confounders.

Allograft inflammatory factor-1-like is not essential for age dependent weight gain or HFD-induced obesity and glucose insensitivity

The allograft inflammatory factor (AIF) gene family consists of two identified paralogs – AIF1 and AIF1-like (AIF1L). The encoded proteins, AIF1 and AIF1L, are 80% similar in sequence and show conserved tertiary structure. While studies in human populations suggest links between AIF1 and metabolic diseases such as obesity and diabetes, such associations with AIF1L have not been reported. Drawing parallels based on structural similarity, we postulated that AIF1L might contribute to metabolic disorders, and studied it using mouse models. Here we report that AIF1L is expressed in major adipose depots and kidney but was not detectable in liver or skeletal muscle; in notable contrast to AIF1, AIF1L was also not found in spleen. Studies of AIF1L deficient mice showed no obvious postnatal developmental phenotype. In response to high fat diet (HFD) feeding for 6 or 18 weeks, WT and AIF1L deficient mice gained weight similarly, showed no differences in fat or lean mass accumulation, and displayed no changes in energy expenditure or systemic glucose handling. These findings indicate that AIF1L is not essential for the development of obesity or impaired glucose handling due to HFD, and advance understanding of this little-studied gene and its place in the AIF gene family.

Levels of Adiponectin Expression in Peri-Renal and Subcutaneous Adipose Tissue and Its Determinants in Human Biopsied Samples.

Background: The interactions of adipose tissue with the kidney are hypothesized to affect kidney function. Also, excessive peri-renal fat may increase the risk of cardiometabolic risk. However, the role(s) of peri-renal fat adipocytokine has never been evaluated.Objectives: To elucidate levels of adiponectin expression in peri-renal and subcutaneous adipose tissue and its determinants in human biopsied samples.Methods: A pair of subcutaneous and perirenal fat tissue samples were collected from 80 patients (men: 54; women: 26) who underwent urological operations. Subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area and peri-renal adipose tissue (RAT) volume were quantified on abdominal computed tomography. Cytokine/adipocytokine expression was evaluated by real-time semi-quantitative polymerase chain reaction (qPCR). Probability was considered significant if P < 0.05.Results: Current study evaluated determinants of plasma adiponectin levels and expression levels of adiponectin in SAT and RAT in human samples. We found that: first, plasma adiponectin levels were correlated with VAT area but not with BMI, waist circumference, SAT area, and RAT volume; second, expression levels of adiponectin in SAT were correlated with BMI, waist circumference, and SAT area but not with VAT area and RAT volume; and third, expression levels of adiponectin in RAT were correlated with all adiposity indices including BMI, waist circumference, SAT area, VAT area, and RAT volume.Conclusion: This study evaluated levels of adiponectin expression in RAT and SAT and its determinants in patients who underwent urological operation. Levels of adiponectin mRNA in RAT were negatively correlated with remote fat mass in SAT and VAT and also with local fat mass in RAT, while level of adiponectin in SAT was not correlated with RAT volume. Further studies are warranted to evaluate roles of peri-renal fat mass accumulation and its pathophysiological machineries.

Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss.

Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.

The Many Facets of Erythropoietin Physiologic and Metabolic Response.

In mammals, erythropoietin (EPO), produced in the kidney, is essential for bone marrow erythropoiesis, and hypoxia induction of EPO production provides for the important erythropoietic response to ischemic stress, such as during blood loss and at high altitude. Erythropoietin acts by binding to its cell surface receptor which is expressed at the highest level on erythroid progenitor cells to promote cell survival, proliferation, and differentiation in production of mature red blood cells. In addition to bone marrow erythropoiesis, EPO causes multi-tissue responses associated with erythropoietin receptor (EPOR) expression in non-erythroid cells such neural cells, endothelial cells, and skeletal muscle myoblasts. Animal and cell models of ischemic stress have been useful in elucidating the potential benefit of EPO affecting maintenance and repair of several non-hematopoietic organs including brain, heart and skeletal muscle. Metabolic and glucose homeostasis are affected by endogenous EPO and erythropoietin administration affect, in part via EPOR expression in white adipose tissue. In diet-induced obese mice, EPO is protective for white adipose tissue inflammation and gives rise to a gender specific response in weight control associated with white fat mass accumulation. Erythropoietin regulation of fat mass is masked in female mice due to estrogen production. EPOR is also expressed in bone marrow stromal cells (BMSC) and EPO administration in mice results in reduced bone independent of the increase in hematocrit. Concomitant reduction in bone marrow adipocytes and bone morphogenic protein suggests that high EPO inhibits adipogenesis and osteogenesis. These multi-tissue responses underscore the pleiotropic potential of the EPO response and may contribute to various physiological manifestations accompanying anemia or ischemic response and pharmacological uses of EPO.

Body Composition During Pregnancy Differs by Obesity Class.

The aim of this study is to characterize changes in body composition during pregnancyin women with obesity. Fifty-four healthy women with obesity (class 1, 30-34.9 kg/m2 : n = 25; class 2, 35-39.9 kg/m2 : n = 21; class 3, ≥ 40.0 kg/m2 : n = 8) expecting a singleton pregnancy were studied. Body composition was measured in earlypregnancy (13-16 weeks), midpregnancy (24-27 weeks), and late pregnancy (35-37 weeks) using air displacement plethysmography, stable isotopes, and skinfold thickness measurements. Fasting glucose, insulin, and leptin were measured. The gain in fat-free mass was lower in the second trimester compared with the third (2.7 ± 0.2 to 5.3 ± 0.2 kg; P < 0.001), whereas fat mass accumulation declined over time (0.6 ± 0.3 to -0.7 ± 0.4 kg; P = 0.005). Women with class 1 and 2 obesity gained 1.1 ± 0.7 kg offat mass during pregnancy, while women with class 3 obesity lost 4.1 ± 0.6 kg (both P < 0.001). The difference in fat accumulation between obesity classes was observed only in the second trimester (P = 0.02). Gestational weight gainwas associated positively with changes in plasma concentrations of insulin, leptin, and insulin resistance (all P < 0.01). Gestational weight gain in pregnancy differs by obesity class and trimester. Women with class 3 obesity gain less body weight and fat mass. Fat mass gain is most likely preventable in the second trimester.

Energy Intake Requirements in Pregnancy.

Energy intake requirements in pregnancy match the demands of resting metabolism, physical activity, and tissue growth. Energy balance in pregnancy is, therefore, defined as energy intake equal to energy expenditure plus energy storage. A detailed understanding of these components and their changes throughout gestation can inform energy intake recommendations for minimizing the risk of poor pregnancy outcomes. Energy expenditure is the sum of resting and physical activity-related expenditure. Resting metabolic rate increases during pregnancy as a result of increased body mass, pregnancy-associated physiological changes, i.e., cardiac output, and the growing fetus. Physical activity is extremely variable between women and may change over the course of pregnancy. The requirement for energy storage depends on maternal pregravid body size. For optimal pregnancy outcomes, women with low body weight require more fat mass accumulation than women with obesity, who do not require to accumulate fat mass at all. Given the high energy density of fat mass, these differences affect energy intake requirements for a healthy pregnancy greatly. In contrast, the energy stored in fetal and placental tissues is comparable between all women and have small impact on energy requirements. Different prediction equations have been developed to quantify energy intake requirements and we provide a brief review of the strengths and weaknesses and discuss their application for healthy management of weight gain in pregnant women.