Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice

High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity

Testosterone and cortisol do not predict rejecting harm or maximizing outcomes in sacrificial moral dilemmas: a preregistered analysis

Contemporary moral psychology explores the biological underpinnings of morality, including how neuromodulators influence moral judgment and decision making. Some studies suggest that higher circulating testosterone is associated with increased acceptance of sacrificial harm, such as killing one person to save five lives, consistent with utilitarian ethics and inconsistent with deontological ethics. However, most studies employ conventional analytic techniques that conflate concern about outcomes with reduced concern about sacrificial harm, many are statistically underpowered, and none examine potential regulating effects of cortisol. Therefore, we examined whether salivary concentrations of testosterone and cortisol jointly predict sacrificial dilemma judgments among a large sample of undergraduates (n = 199). We utilized an advanced cognitive modeling technique (process dissociation) to independently assess sensitivity to causing harm and maximizing outcomes, preregistering the prediction that higher testosterone would predict reduced harm-rejection rather than increased concern for outcomes, especially among people low in cortisol. However, neither testosterone, nor cortisol, nor their interaction predicted sacrificial dilemma response tendencies. Such findings raise questions about the robustness of past evidence suggesting links between testosterone and sacrificial dilemma judgments

CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage

Although there are numerous benefits to having a satisfying romantic relationship, maintaining high levels of relationship satisfaction is difficult. Many couples experience declines in relationship satisfaction in the early years of marriage, and such declines predict not only relationship dissolution but also poor mental and physical health. Several recent studies indicate that genetic variation on the CD38 gene (CD38), at the single nucleotide polymorphism (SNP) rs3796863, is associated with cognitions and behaviors related to pair bonding; we thus leveraged longitudinal data from a sample of newlywed couples (N = 139 genotyped individuals; 71 couples) to examine whether rs3796863 is associated with relationship maintenance processes and, in turn, relationship satisfaction in the early years of marriage. Replicating and extending prior research, we found that individuals with the CC genotype (vs. AC/AA) of rs3796863 reported higher levels of gratitude, trust, and forgiveness and that trust mediated the association between rs3796863 and marital satisfaction. Moreover, the benefits conferred to CC individuals lasted over the first 3 years of marriage. To our knowledge, this is the first study to examine the link between variation in CD38 rs3796863 and marital functioning over time

Induction of Salivary Proteins Modifies Measures of Both Orosensory and Postingestive Feedback during Exposure to a Tannic Acid Diet - Figure 4

<p>A–D: White bars represent feeding behaviors measured while animals were consuming the control diet; grey bars represent the same behaviors measured while animals were on the 3% tannic acid diet. The white bar labeled ‘C’ represents a 5-day average of behavioral measures on the control diet prior to exposure to the tannic acid diet. Food intake (A) and meal size (B) were decreased on the first 3 days of exposure to the tannic acid diet but returned to control levels by day 4. Meal number (C) was increased during the first 2 days of exposure to the tannic acid diet but returned to control-levels by day 3. Rate of feeding (D) was decreased throughout the entire exposure to the tannic acid diet buy this effect was most pronounced during the first 3 days.</p

Coordinated Gene Expression

<p>Regression analyses of SFRP5, MEST, and Naked mRNA levels in RNA isolated from high and low gainer mice in inguinal fat depots suggest that regulation of this subset of genes share a common mechanism related to the degree of adiposity. Twenty mice were present in each group.</p

Over-Expression of Four Genes in High Gainer Mice in Two Peritoneal Fat Depots and One Subcutaneous Fat Depot Illustrates that the Mechanism Leading to Over-Expression of These Genes Occurs in All Fat Depots

<p>Statistical significance was calculated by ANOVA. Twenty mice were present in each group.</p

Establishing Variations in Adiposity in Diet-Induced Obesity in Male C57BL/6J Mice

<p>Frequency distribution of body weight in 219 mice at 12 wk of age, after being fed a high-fat diet for 4 wk. (A) Regression analysis between the change in body weight and fat mass (B) and change in body weight and lean body mass (C) from 8 and 12 wk of age as determined by NMR in 112 mice. (D) Regression analysis between mouse weight at weaning and the percent change of the ratio of fat mass (FM) to lean mass (LM) per week, <i>p</i> = .0105, <i>n</i> = 220. Changes in the FM/LM ratio per wk were calculated from 8–12 wk of age or from 8–14 wk of age. (E) Average percent change of the ratio of FM/LM per week for the various litter sizes, <i>p</i> = .0406, <i>n</i> = 220 (ANOVA).</p

The closed circles represent the average licking of the two test groups during their first exposure to the brief-access test (unconditioned licking does not differ between the groups at this time point p>0.05).

<p>The open circles represent the average licking during the second exposure to the brief-access test by rats that were maintained on the control diet. The open triangles represent the average licking during the second exposure to the brief-access test by rats that were maintained on the tannic acid diet between exposures. Lines represent curves fit to the average licking behavior. Rats with an increase in the salivary protein at 19/18.5 and 18 kDa bands show a right-ward shift in the licking response curve demonstrating that they found the tannic acid less aversive in the second exposure than the first exposure, while rats maintained on the control diet did not alter their licking behavior on the second exposure.</p

Stability of the Adiposity Phenotype in B6 Mice

<p>Male mice (<i>n</i> = 107) were fed a low-fat chow diet (Picolab 5053) from weaning to 8 wk of age, a high-fat diet (Research Diets D12331) from 8–14 wk, then the low-fat chow diet, restricted to 80% of the amount consumed from wk 7–8, during wk 15 and16, and finally, the high-fat diet for wk 17–22. Mice were weighed weekly except during the food restriction period when body weights were measured daily until they had stabilized under these conditions. Food intake was measured weekly starting from wk 7. At the end of wk 8, 14, 16, and 22, the body composition of each mouse was analyzed by NMR. The body weight curves of mice at the upper and lower 10% of the frequency distribution at 22 wk of age are plotted in red and blue.</p