Weight Gain Response Research Articles

Estimate of choline nutritional requirements for chicks from 1 to 21 days of age.

Choline is an essential nutrient in poultry diets because it performs various important metabolic functions. The objective of this study was to re-evaluate the choline requirements of male broiler chickens from 1 to 21days of age at two levels of methionine. Two assays using 2,160 Cobb® chickens (1,080 in each assay) were conducted. The study design was completely randomized and consisted of six treatments and six replicates, with 30 animals per experimental unit. The semipurified basal diet was formulated with corn, soya bean meal, soya protein concentrate, starch and sugar, providing 390mg/kg choline and 0.593% digestible methionine (requirement level) in Assay 1 and a reduction of about one-quarter in the requirement level of digestible methionine (0.440%) in Assay 2. Choline chloride (62.5%) was added by a supplementation technique to both basal diets to compose crescent levels of choline supplementation (715, 1,040, 1,365, 1,690 and 2,015mg/kg). The weight gain responses were fitted using quadratic polynomial (QP) and broken-line (BL) models. The ideal intake of choline (mg/bird.day) was estimated from the first intercept of the QP with the BL plateau (BL+QP). The results showed that the diet with the 25% reduction in digestible methionine limited the maximum weight gain by approximately 10%. The choline requirements of broilers from 1 to 7, 1 to 14 and 1 to 21days of age were 27,013, 44,458 and 62,535mg/bird.day, respectively, for the requirement level of digestible methionine and 26,796, 41,820 and 56,578mg/bird.day for the broilers receiving the diet with the 25% reduction in digestible methionine.

JIP3 knockout protects mice against high fat diet-induced liver injury

Multiple pathways contribute to nonalcoholic fatty liver disease (NAFLD) in response to high fat diets (HFD). A homolog of mammalian JNK-interacting protein 3 (JIP3), also known as JSAP-1, activates different components in various signaling pathways to modulate cellular processes. The purpose of this study was to examine the role of JIP3 in obesity-related pathologies pathway. Wild-type (WT) C57BL/6 and JIP3-knockout (JIP3−/−) mice were randomized to chow or HFD. HFD-fed WT mice increased hepatic JIP3 expression. Mice lacking JIP3 exhibited reduced weight gain, hepatic steatosis, insulin resistance, lipid accumulation, oxidative stress and inflammatory response in mice fed a HFD, which were, importantly, dependent on various signaling pathways. Lipogenesis-linked pathway was inhibited in JIP3−/− mice after HFD, while PPARα/γ were increased. Additionally, JIP3−/− inhibited hepatic oxidative stress, evidenced by down-regulation of total reactive oxygen species (ROS), H2O2, O2.-, malondialdehyde (MDA), xanthine oxidase (XO), inducible nitric oxide synthase (iNOS), and up-regulation of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in mice after HFD feeding, which might be related to nuclear respiratory factor 2 (Nrf-2) pathway activation. Further, inflammatory response was blocked in JIP3−/− mice fed with HFD. The process might be attributed to the suppression of toll-like receptors (TLRs), p-nuclear factor kappa B (NF-κB) and p-c-Jun-N-terminal kinase (JNK). Thus, JIP3 absence is associated with decreased lipogenesis, oxidative stress and inflammation, supplying a new target for NAFLD treatment.

Growth Performance of the African catfish, Clarias gariepinus, Fed Varying Inclusion Levels of Allium sativum as Feed Additives

Diet supplementation is an important aspect in aquaculture management especially in intensive or in semi-intensive fish culture. An experiment was conducted to evaluate the effect of Allium sativum on growth performance of African catfish, Clarias gariepinus fries. Four experimental diets were formulated to include Allium sativum powder at 0% (control), 0.5%, 1.0%, and 3.0% as additives. All the four treatment diets were fed to African catfish (Clarias gariepinus) fries over a 70-day period. The result showed a similar (P>0.05) growth responses across the groups. However, the best growth response in body weight gain of 1.44 ± 0.07g, Specific Growth Rate (SGR) of 0.52 ± 0.03g and Feed conversion Ratio (FCR) of 5.60 ± 0.38 was obtained in fish fed 3.0% Allium sativum inclusion level while the best condition factor (K) was observed in fish fed 0.5 % Allium sativum inclusion level. Fish fed 0.0% Allium sativum had the lowest growth response of body weight gain, Specific Growth Rate (SGR), Feed conversion Ratio (FCR) and condition factor of 0.84 ± 0.11g, 0.36 ± 0.03g, 5.77 ± 0.53 and 0.80 ± 0.03 respectively. Garlic inclusion in fish diet at 3.0% (30g/kg) concentration is therefore beneficial for use in aquaculture to enhance growth promotion however a further research is recommended to investigate toxicity of this plant at varying inclusion levels of 0.5% to 3.0% in the Clarias gariepinus culturing to ascertain the best inclusion level.

Effect of dietary supplements in American bullfrogs reared in low and high stocking densities

The aim of this study was to evaluate the effect of the probiotic Bacillus subtillis and beta-glucan from the fungus Agaricus blazei on survival, growth and immunological capacity in bullfrogs (Lithobates catesbeianus) cultured in low and high stocking densities. Animals weighing 24.3±2.38g were randomly distributed into four treatments with four simultaneous replicates: D100: 100 frogs/m2 (control); D236: 236 frogs/m2; D236+Prob.: 236 frogs/m2 supplemented with probiotic; and D236+BG: 236 frogs/m2 supplemented with beta-glucan. The parameters evaluated were weight gain, survival, plasma corticosterone (CORT), phagocytic capacity (PC) and phagocytic index (PI), at 24h and 15 and 30days. There is significant interaction between treatments and time for CORT levels. At 30days, these values were very close for the D100 (control) and D236+BG groups. Meanwhile, no statistical differences were observed between treatments for PC and PI. These results indicate that beta-glucan reduced the effects of stress caused by high density in bullfrogs, but the probiotic did not reduce these effects. Both compounds are not efficient at increasing survival rates, weight gain and neither immune response of animals. Thus, the use of commercial food additives may not have the favorable impact desired by the farmer. Their use in aquaculture should be further studied in experiments involving a longer trial period and taking into account the cost of their use.

Growth performance, nutrient utilisation and carcass composition respond to dietary protein concentrations in broiler chickens but responses are modified by dietary lipid levels.

A total of ten experimental diets with protein concentrations ranging from 154 to 400 g/kg and two lipid levels (46 and 85 g/kg) with identical energy densities were offered to 240 male Ross 308 broilers from 7 to 28 d post-hatch. Growth performance was monitored and nutrient utilisation (apparent metabolisable energy (AME), N-corrected AME (AMEn), AME daily intake, AME:gross energy ratios, N retention) was determined. The weight gain response of broiler chickens to dietary protein concentrations in diets containing high and low lipid levels was diverse, with the relevant quadratic regressions being significantly different (P0·05). AMEn was also linearly (P<0·0001) increased with dietary protein concentrations but regressions in diets with low and high lipid content were significantly different (P<0·03). Carcass protein content increased linearly with dietary protein content in diets containing high lipid concentrations (r 0·933, P<0·0001); by contrast, this relationship was quadratic (R 2=0·93, P<0·0001) in diets with low lipid levels. In conclusion, predictably, the effects of dietary protein concentrations on broiler performance were profound; however, the impact of dietary protein on performance in broiler chickens was modified by dietary lipid concentrations.

Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity

Diet-induced thermogenesis is an important homeostatic mechanism that limits weight gain in response to caloric excess and contributes to the relative stability of body weight in most individuals. We previously demonstrated that creatine enhances energy expenditure through stimulation of mitochondrial ATP turnover, but the physiological role and importance of creatine energetics in adipose tissue have not been explored. Here, we have inactivated the first and rate-limiting enzyme of creatine biosynthesis, glycine amidinotransferase (GATM), selectively in fat (Adipo-Gatm KO). Adipo-Gatm KO mice are prone to diet-induced obesity due to the suppression of elevated energy expenditure that occurs in response to high-calorie feeding. This is paralleled by a blunted capacity for β3-adrenergic activation of metabolic rate, which is rescued by dietary creatine supplementation. These results provide strong invivo genetic support for a role of GATM and creatine metabolism in energy expenditure, diet-induced thermogenesis, and defense against diet-induced obesity.

Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.

Sufficient sleep is required for weight maintenance. Sleep deprivation due to noise exposure stimulates weight gain by increasing hyperphagia and reducing energy expenditure (EE). Yet the mechanistic basis underlying the weight gain response is unclear. Orexin-A promotes arousal and negative energy balance, and orexin terminals project to the ventrolateral preoptic area (VLPO), which is involved in sleep-to-wake transitions. To determine whether sleep deprivation reduces orexin function in VLPO and to test the hypothesis that sleep deprivation would attenuate the orexin-A-stimulated increase in arousal, physical activity (PA), and EE. Electroencephalogram, electromyogram, distance traveled, and EE were determined in male Sprague-Dawley rats following orexin-A injections into VLPO both before and after acute (12-h) and chronic (8 h/d, 9 d) sleep deprivation by noise exposure. Orexin-A in the VLPO significantly increased arousal, PA, total EE, and PA-related EE and reduced sleep and respiratory quotient before sleep deprivation. In contrast to after acute sleep deprivation in which orexin-A failed to stimulate EE during PA only, orexin-A failed to significantly increase arousal, PA, fat oxidation, total EE, and PA-related EE after chronic sleep deprivation. Sleep deprivation may reduce sensitivity to endogenous stimuli that enhance EE due to PA and thus stimulate weight gain.

Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat.

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow.

Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection

It has been shown that inter-individual variation in host response to porcine reproductive and respiratory syndrome (PRRS) has a heritable component, yet little is known about the underlying genetic architecture of gene expression in response to PRRS virus (PRRSV) infection. Here, we integrated genome-wide genotype, gene expression, viremia level, and weight gain data to identify genetic polymorphisms that are associated with variation in inter-individual gene expression and response to PRRSV infection in pigs. RNA-seq analysis of peripheral blood samples collected just prior to experimental challenge (day 0) and at 4, 7, 11 and 14 days post infection from 44 pigs revealed 6,430 differentially expressed genes at one or more time points post infection compared to the day 0 baseline. We mapped genetic polymorphisms that were associated with inter-individual differences in expression at each day and found evidence of cis-acting expression quantitative trait loci (cis-eQTL) for 869 expressed genes (qval < 0.05). Associations between cis-eQTL markers and host response phenotypes using 383 pigs suggest that host genotype-dependent differences in expression of GBP5, GBP6, CCHCR1 and CMPK2 affect viremia levels or weight gain in response to PRRSV infection.

Estimation of optimal ratios of digestible phenylalanine + tyrosine, histidine, and leucine to digestible lysine for performance and breast yield in broilers

Three experiments were carried out to estimate the optimal ratios of digestible phenylalanine + tyrosine (Phe + Tyr), histidine (His), and leucine (Leu) relative to digestible lysine (Lys) for performance and carcass criteria of Cobb-500 broilers from 8 to 17 d of age. In each experiment, 160 male chicks were allocated to a completely randomized experimental design with eight replicate pens, each receiving five dietary treatments. A common, semi-purified basal diet was formulated to meet all dietary recommendations except for those of the tested amino acids (i.e., Phe + Tyr, His, and Leu). Growth performance and carcass characteristics data were analyzed using various requirement-estimation models, including 95% of the quadratic regression, linear response plateau (LRP; i.e., stepwise regression), LRP-to-quadratic regression ratio; and quadratic broken line (QBL). Graded digestible Phe + Tyr ratios elicited a quadratic response (P < 0.05) in body weight gain and linear responses (P < 0.05) in breast and breast fillet weights. Linear effects (P < 0.05) were also observed when graded ratios of digestible His were fed for feed intake and weight gain, and quadratic responses (P < 0.05) were noted for feed conversion ratio and breast and breast fillet weights and yields. Graded Leu ratios elicited quadratic responses (P < 0.05) in feed intake, weight gain, and breast and breast fillet weight and yield. Based on growth and carcass parameters, the estimated ideal digestible ratios of Phe + Tyr, His, and Leu relative to digestible Lys were 112, 38, and 104%, respectively, for broiler chicks raised from 8 to 17 d of age.

Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background.

The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male C57BL/6J mice on the HiE diets ate less, whereas males on the HiE diets compared with the STD diets gained weight. All diet treatments reduced energy expenditure in females but in males only those on the HiE + O diet. Gut microbiota composition differed in the C57BL/6J females but not the males. Hybrid B6SJLF1/J mice showed similar weight gain on all test diets. In contrast, mixed strain male mice fed a HiE + O diet gained ∼40% more weight than females on the same diet. In addition to increased weight gain, mixed genetic mice on the HiE + O diet cleared glucose normally but secreted more insulin. We concluded that sex and genetic background define weight gain and metabolic responses of mice on high caloric diets and OM.

Expression profile of hepatic genes related to lipid homeostasis in LSR heterozygous mice contributes to their increased response to high-fat diet.

Perturbations of lipid homeostasis manifest as dyslipidemias and obesity, which are significant risk factors for atherosclerosis and diabetes. Lipoprotein receptors in the liver are key players in the regulation of lipid homeostasis, among which the hepatic lipolysis stimulated lipoprotein receptor, LSR, was recently shown to play an important role in the removal of lipoproteins from the circulation during the postprandial phase. Since heterozygous LSR+/- mice demonstrate moderate dyslipidemia and develop higher body weight gain in response to high-fat diet compared with littermate LSR+/+ controls, we questioned if LSR heterozygosity could affect genes related to hepatic lipid metabolism. A target-specific qPCR array for 84 genes related to lipid metabolism was performed on mRNA isolated from livers of 6 mo old female LSR+/- mice and LSR+/+ littermates following a 6 wk period on a standard (STD) or high-fat diet (60% kcal, HFD). Of the 84 genes studied, 32 were significantly downregulated in STD-LSR+/- mice compared with STD-LSR+/+, a majority of which were PPARα target genes involved in lipid metabolism and transport, and insulin and adipokine-signaling pathways. Of these 32 genes, 80% were also modified in HFD-LSR+/+, suggesting that STD-LSR+/- mice demonstrated a predisposition towards a "high-fat"-like profile, which could reflect dysregulation of liver lipid homeostasis. Since similar profiles of genes were affected by either LSR heterozygosity or by high-fat diet, this would suggest that LSR is a key receptor in regulating hepatic lipid homeostasis, and whose downregulation combined with a Western-type diet may increase predisposition to diet-induced obesity.

Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice

The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N-linked glycans on the β - subunit) FSH. The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time-dependent manner. Quantification by real time qPCR assays indicated that hypo-glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully-glycosylated FSH24 in ovaries of Fshb null mice. When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms.

Whey protein increases muscle weight gain through inhibition of oxidative effects induced by resistance exercise in rats

Whey protein (WP) is known for its nutritional value and antioxidant properties. The aim of this study was to evaluate whether the antioxidant properties of WP could contribute to muscle weight gain in response to resistance exercise (RE). We hypothesized that WP ingestion could increase muscle weight gain in rats subjected to an RE program, through inhibition of oxidative effects induced by high-intensity RE. Thirty-two male Fischer rats were randomly assigned to control sedentary, control exercised, WP sedentary, and WP exercised groups (n=8/group). The RE consisted of inducing the rats to perform sets of jumps for 8 weeks. Body and muscle weight gains, muscle glutathione content, histopathology, muscle antioxidant enzyme activities, and gene expression were evaluated. Body and muscle weight gains of exercised rats fed WP were higher than those of control exercised rats. Concomitantly, RE induced an increase in phagocyte infiltration, protein oxidation, and down-regulation of glutathione peroxidase and gamma-glutamylcysteine synthetase messenger RNA expression in gastrocnemius muscle (P<.05), effects that were inhibited by WP ingestion. Cytosolic superoxide dismutase and catalase messenger RNA expression were reduced only by RE (P<.05), and muscle glutathione content was increased only by WP (P<.05) with no significant interaction observed (P>.05). These findings suggest that differences in body and muscle weight gain in exercised rats fed control or WP diets were mediated, in part, by the antioxidant properties of WP, and indicate that when associated with RE, WP represents a nutritional aid to support muscle growth.

Effect of respiratory vaccine components and route of delivery on weight gain and inflammatory response in suckling beef calves

Two randomized studies of Angus beef calves (n = 110) from 2 Iowa locations were used to determine the effect of vaccine type and route of administration on weight gain and inflammatory response. The first vaccine contained avirulent-live Mannheimia haemolytica (type A1) and Pasteu- rella multocida (type A3), and was administered intranasally (IN group). The second vaccine contained an adjuvanted M. haemolytica (type Al) toxoid and was administered subcutaneously (SC group). Control calves (CON) were given the same volume (2 mL) of sterile saline SC as other calves. At the time of vaccination (day 0), calf body weight (BW) and body temperature (BT) were recorded, and a blood sample was collected for serum haptoglobin analysis. Blood collection and BT measurement were repeated on days 1, 2, and 3 while BW was recorded on days 3 and 21 (location 1) or 24 (location 2) after vaccination. A final BW was taken at weaning at both locations. Changes in BW among calves during the first 3 days after vaccination were not significantly different across treatment groups. At location 1, calves given SC vaccine had a higher average BT compared to IN-vaccinated calves (P &lt; 0.01). Body temperature also tended to be higher in SC-vaccinated calves (P = 0.08) compared to CON calves. At location 2, BT was not different between vaccinated groups, but vaccinated calves had higher BT compared to CON calves (P&lt; 0.01). Over the 21-day trial period at location 1, average daily gain (ADG) in calves given SC vaccine was lower compared to CON calves (P = 0.04). At location 2, ADG was not significantly different among treatments, but IN calves had heavier final weights compared to other treatment groups (P &lt; 0.01). Serum haptoglobin levels were higher for SC calves compared to IN and CON calves on days 1, 2, and 3 following vaccination (P &lt; 0.01). Mean weight gain and ADG from vaccination through weaning tended to be greater (P = 0.06) for IN calves at location 1, but were not different at location 2.

Role of the vagus nerve in the development and treatment of diet-induced obesity.

This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity.

Pancreatic β-Cell Dysfunction in Diet-Induced Obese Mice: Roles of AMP-Kinase, Protein Kinase Cε, Mitochondrial and Cholesterol Metabolism, and Alterations in Gene Expression.

Diet induced obese (DIO) mice can be stratified according to their weight gain in response to high fat diet as low responders (LDR) and high responders (HDR). This allows the study of β-cell failure and the transitions to prediabetes (LDR) and early diabetes (HDR). C57BL/6N mice were fed for 8 weeks with a normal chow diet (ND) or a high fat diet and stratified as LDR and HDR. Freshly isolated islets from ND, LDR and HDR mice were studied ex-vivo for mitochondrial metabolism, AMPK activity and signalling, the expression and activity of key enzymes of energy metabolism, cholesterol synthesis, and mRNA profiling. Severely compromised glucose-induced insulin secretion in HDR islets, as compared to ND and LDR islets, was associated with suppressed AMP-kinase activity. HDR islets also showed reduced acetyl-CoA carboxylase activity and enhanced activity of 3-hydroxy-3-methylglutaryl-CoA reductase, which led respectively to elevated fatty acid oxidation and increased cholesterol biosynthesis. HDR islets also displayed mitochondrial membrane hyperpolarization and reduced ATP turnover in the presence of elevated glucose. Expression of protein kinase Cε, which reduces both lipolysis and production of signals for insulin secretion, was elevated in DIO islets. Genes whose expression increased or decreased by more than 1.2-fold were minor between LDR and ND islets (17 differentially expressed), but were prominent between HDR and ND islets (1508 differentially expressed). In HDR islets, particularly affected genes were related to cell cycle and proliferation, AMPK signaling, mitochondrial metabolism and cholesterol metabolism. In conclusion, chronically reduced AMPK activity, mitochondrial dysfunction, elevated cholesterol biosynthesis in islets, and substantial alterations in gene expression accompany β-cell failure in HDR islets. The β-cell compensation process in the prediabetic state (LDR) is largely independent of transcriptional adaptive changes, whereas the transition to early diabetes (HDR) is associated with major alterations in gene expression.

Continuous Glucose Measurements Using Telemetry in Male and Female Dahl Salt‐Sensitive Rats (DSS) on a High‐Fat Diet

The HD‐XG glucose telemetry implant from DSI provides the ability to obtain continuous, real‐time, blood glucose measurements in rodents. The goal of the current study was to compare spot blood glucose measurements with values obtained using telemetry in male and female DSS. Male and female rats were implanted with glucose telemeters at 11 weeks of age, and allowed 1 week to recover before being placed on receivers. Rats were maintained on a normal‐salt, normal‐fat (NF; 16% caloric intake from fat) diet for 1 week and then were switched to a high‐fat diet (HF; 65% caloric intake from fat) for 4 weeks (n=4–5/group sex). Additional rats without telemeter implants were maintained on normal‐salt, normal‐fat diet for the duration of the experiment. All rats gained weight over the 4 week treatment period, however, rats of both sexes on a HF diet exhibited a significantly greater increase in body weight compared to rats on NF (males: 15±1% on NF vs. 22±2% on HF, p&lt;0.05; females: 12±1% on NF vs. 18±2% on HF, p&lt;0.05). There was not a sex difference in weight gain in response to HF diet. Mean absolute relative differences in blood glucose as measured by the HD‐XG compared to spot glucose ranged from 0.1% up to 4.8% in males and 0.7% up to 8.9% in females, indicating that the 2 measurements were always within 10% of one another. Baseline blood glucose levels in male and female DSS measured by HD‐XG were comparable (109±2 vs. 111±2 mg/dL, respectively). HF diet for 4 weeks did not significantly alter blood glucose levels in either sex (male: 106±3 mg/dL; female: 104±4 mg/dL). Additionally, average weekly glucose for both sexes were statistically identical whether analyzed over 24 hour periods or limited to only the light or dark periods. From this study we can conclude the following: 1) glucose telemeters are a reliable methods to obtain continuous measurements of blood glucose in male and female rats, 2) there are no sex differences in blood glucose following a 4 week HF diet in DSS, and 3) DSS are able to tolerate a HF diet with minimal alterations in body weight or blood glucose.

Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia.

Association between weight gain and sarcopenic obesity in patients treated with androgen deprivation therapy.

189 Background: Weight gain in response to androgen deprivation therapy (ADT) can be a marker for adverse effects of ADT. However, a concomitant decrease in lean mass in response to ADT may decrease the utility of weight gain in terms of sarcopenia. Therefore, the goal of the present study was to analyze the relationship among weight gain, obesity, and sarcopenia in patients undergoing ADT. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and results from blood tests of lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat and the psoas muscle before and after 1-year of ADT. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Results: CT was performed in 72 patients before and after 1 year of ADT. Median age was 74 years (49-83). Median prostate-specific antigen before ADT was 21.9 ng/ml (0.3-3316). Clinical stage was B (43.1%), C (26.4%), and D (29.2%). Mean increase in weight was 2.7% after 1 year of ADT. Mean increase in the area of subcutaneous and visceral fat was 31.3% and 20.7%, respectively. Mean change in the area of the psoas muscle was -8.4%. When patients were divided into two groups according to weight change during 1 year of ADT (Group A (n = 34): weight gain &lt; 3.0%, Group B (n = 38): weight gain ≥ 3.0%), an increase in subcutaneous and visceral fat was significantly more frequent in Group B, whereas the frequency of a decrease in psoas muscle area was not significantly different between the two groups (Group A: -9.5%, Group B: -7.5%, P = 0.11). Pearson correlation coefficients showed a moderate relationship between weight gain and fat accumulation (r = 0.44-0.52), but little relationship between weight gain and a decrease in psoas muscle area (r = 0.18). Conclusions: Fat accumulation tended to increase in patients who gained weight during ADT, whereas a decrease in psoas muscle area was not related to weight change. Sarcopenia could occur despite weight change during ADT. Clinical trial information: UMIN000018478.