Effect of variants in the ovine skeletal-muscle-specific calpain gene on body weight

The ovine skeletal-muscle-specific calpain gene (p94), which is known also as the n-calpain or calpain 3 gene (CAPN3), was screened with primers. Selection of the PCR primers was based on the ovine cDNA sequence (GenBank accession No. AF087570). After sequence alignment between the ovine and human (AY902237) genes, exon and intron boundaries were determined. Polymorphisms were observed in the intron region for the CAPN31112 and CAPN31213 segments, and the sequences for these segments were submitted to the GenBank (AF309635 and AY102617, respectively). Body weight was recorded at birth, weaning and post-weaning. Calpain 3 genotypes of the CAPN31112 segment were associated with birth weight (P < 0.01), and a dominant gene effect was observed. Breeding group, birth type, and rearing type were significantly associated with weight traits. Allele frequencies were similar in purebred and crossbred animals.     

Molecular basis of selective PPARgamma modulation for the treatment of Type 2 diabetes

Peroxisome proliferator-activated receptors (PPARs) (alpha, beta/delta and gamma) are lipid sensors capable of adapting gene expression to integrate various lipid signals. As such, PPARs are also very important pharmaceutical targets, and specific synthetic ligands exist for the different isotypes and are either currently used or hold promises in the treatment of major metabolic disorders. In particular, compounds of the class of the thiazolinediones (TZDs) are PPARgamma agonists and potent insulin-sensitizers. The specific but still broad expression patterns of PPARgamma, as well as its implication in numerous pathways, constitutes also a disadvantage regarding drug administration, since this potentially increases the chance to generate side-effects through the activation of the receptor in tissues or cells not affected by the disease. Actually, numerous side effects associated with the administration of TZDs have been reported. Today, a new generation of PPARgamma modulators is being actively developed to activate the receptor more specifically, in a cell and time-dependent manner, in order to induce a specific subset of target genes only and modulate a restricted number of metabolic pathways. We will discuss here why and how the development of such selective PPARgamma modulators is possible, and summarize the results obtained with the published molecules.     

Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity

Obesity-associated diabetes is epidemic in industrialized societies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in adipose tissue and the presumed molecular target for antidiabetic thiazolidinedione drugs that reverse insulin resistance but also promote weight gain. Phosphorylation reduces the activity of PPARgamma in vitro, but physiological relevance has not been demonstrated. We have studied mice homozygous for a mutation (S112A) that prevents PPARgamma phosphorylation. Surprisingly, the weights and adipose mass of PPARgamma-S112A mice are not greater than wild-type. Remarkably, however, genetic prevention of PPARgamma phosphorylation preserves insulin sensitivity in the setting of diet-induced obesity. Underlying this protection are smaller fat cells, elevated serum adiponectin, and reduced free fatty acid levels. Thus, the phosphorylation state of PPARgamma modulates insulin sensitivity. Compounds that prevent PPARgamma phosphorylation or ligands that induce the conformation of nonphosphorylated PPARgamma may selectively enhance insulin sensitivity without increasing body weight.     

Plasma triglyceride levels correlate with body weight,age and gender influence body weight changes in Spermophilus lateralis during prehibernation and hibernation

Our experimental groups consisted of a total 16 male (M) and 15 female (F), juvenile and adult Spermophilus lateralis. This study evaluated weight gain rate (WGR) and mass-specific rate of gain (MSRG) during prehibernation, and weight loss rate (WLR), mass-specific rate of loss (MSRL) plus changes in the levels of plasma triglyceride (TG) during hibernation in these squirrels (SQ). Between January and March, the plasma samples were obtained from 26 SQ. Plasma TG was determined enzymatically, and it averaged 189 mg% with no significant difference in gender. Correlations were observed between plasma TG and sacrificed body weight (r = 0.441, p < 0.05), and between plasma TG and MSRL (r = 0.409, p < 0.05), although plasma TG was not correlated with WLR during hibernation. Juvenile female SQ had a higher WGR than adult female SQ, but no significant difference was found between juvenile and adult males. Both juvenile males and females showed a significantly higher MSRG than adult male and female SQ. Conversely, adult male SQ had a higher WLR and MSRL than juvenile male SQ, but no significant difference was observed between adult and juvenile females. Moreover, juvenile male SQ showed a significantly lower WLR but not MSRL than juvenile females. For these animals, our results suggest that the age factor influences on WGR and MSRG during prehibernation, and also influences on WLR and MSRL during torpor.     

Association between regulator of G protein signaling 9-2 and body weight

Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9-2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9-2 as a factor in regulating body weight.     

Differential modulation of cell cycle, apoptosis and PPARgamma2 gene expression by PPARgamma agonists ciglitazone and 9-hydroxyoctadecadienoic acid in monocytic cells

We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.     

Interaction between the effects of stress and morphine on body temperature in rats

The relation between stress-induced and morphine-induced body temperature changes was examined in rats. Three groups of eight animals thoroughly habituated to handling and rectal probing, and three groups of eight experimentally naive animals were injected intraperitoneally with either 1, 5, or 30 mg/kg morphine sulphate on each of six consecutive days. Differences in temperature readings from the pre-injection baseline showed that on Day 1 of the experiment stress acted to effectively increase the potency of morphine, causing slightly increased hyperthermia at the lowest dose and greatly increased hypothermia at the highest dose. Thus for habituated animals the dose-response curve for morphine was shifted to the right. By Day 6, after repeated morphine injections, all animals showed a hyperthermic response to morphine and the differences between habituated and unhabituated animals had disappeared. These findings were discussed in terms of the interaction between the temperature changes produced by endogenous opioids in stressed animals and the actions of exogenously administered morphine.     

Effect of body fat and gender on body temperature distribution

It is well known that body composition can influence peripheral heat loss and skin temperature. That the distribution of body fat is affected by gender is well known; however, there is little information on how body composition and gender influences the measure of skin temperature. This study evaluated skin temperature distribution according to body fat percentage (BF%) and gender. A sample of 94 apparently healthy volunteers (47 women and 47 men) was assessed with Dual-Energy X-Ray Absorptiometry (DXA) and infrared thermography (mean, maximum and minimum temperatures – T_Mean, T_Max and T_Min). The sample was divided into groups, according to health risk classification, based on BF%, as proposed by the American College of Sports Medicine: Average (n = 58), Elevated (n = 16) or High (n = 20). Women had lower T_Mean in most regions of interest (ROI). In both genders, group High had lower temperature values than Average and Elevated in the trunk, upper and lower limbs. In men, palms and posterior hands had a tendency (p < 0.05) for increased temperature along with increased BF%. T_Mean, T_Max and T_Min of trunk, upper and lower limbs were negatively correlated with BF% and the fat percentage of each segment (upper limbs, lower limbs and trunk). The highest correlations found in women were between posterior trunk and BF% (rho = −0.564, p < 0.001) and, in men, between anterior trunk and BF% (rho = −0.760, p < 0.001). Overall, this study found that women have lower skin temperature than men, which was related with higher BF%. Facial temperature seems not to be influenced by body fat. With the future collection of data on the relationship between BF% and skin temperature while taking into account factors such as body morphology, gender, and ethnicity, we conclude that measurement of BF may be reliably estimated with the use of thermal imaging technology.     

Relation between body height and weight in adult humans

Series of values for body height of adults ranging from 150 to 190 cm and the corresponding body weights for 9 age groups from 15 to 65 a are interrelated by 5 test functions. Results of nonlinear regressions as gained by minimization of the sums of the squares and absolute values of the deviations are summarized in tables for comparison. The last position in the goodness-of-fit is held by the allometric relation W = alpha L beta preceded by the exponential type W = abL. No considerable gain can be realised by taking the expression W = a exp (b Lp). A big step is reached, however, with the change to the form W = W150 + alpha (L-150) beta reducing the linear deviations to about 1/3 or more. Finally the 3-parameter structure W = W A + alpha (L-150) beta yields even closer approximations. Tables with the results for the last 2 relations are given together with a graph for the best approximation.