Gender-specific effects of intrauterine growth restriction on the adipose tissue of adult rats: a proteomic approach.

BACKGROUND: Intrauterine growth restriction (IUGR) may program metabolic alterations affecting physiological functions and lead to diseases in later life. The adipose tissue is an important organ influencing energy homeostasis. The present study was aimed at exploring the consequences of IUGR on the retroperitoneal adipose tissue of adult male and female rats, using a proteomic approach. METHODS AND RESULTS: Pregnant Wistar rats were fed with balanced chow, either ad libitum (control group) or restricted to 50 % of control intake (restricted group) during the whole gestation. The offspring were weaned to ad libitum chow and studied at 4 months of age. Retroperitoneal fat was analyzed by two-dimensional gel electrophoresis followed by mass spectrometry. Both male and female restricted groups had low body weight at birth and at weaning but normal body weight at adulthood. The restricted males had normal fat pads weight and serum glucose levels, with a trend to hyperinsulinemia. The restricted females had increased fat pads weight with normal glucose and insulin levels. The restricted males showed up-regulated levels of proteasome subunit α type 3, branched-chain-amino-acid aminotransferase, elongation 1- alpha 1, fatty acid synthase levels, cytosolic malate dehydrogenase and ATP synthase subunit alpha. These alterations point to increased proteolysis and lipogenesis rates and favoring of ATP generation. The restricted females showed down-regulated levels of L-lactate dehydrogenase perilipin-1, mitochondrial branched-chain alpha-keto acid dehydrogenase E1, and transketolase. These findings suggest impairment of glycemic control, stimulation of lipolysis and inhibition of proteolysis, pentose phosphate pathway and lipogenesis rates. In both genders, several proteins involved in oxidative stress and inflammation were affected, in a pattern compatible with impairment of these responses. CONCLUSIONS: The proteomic analysis of adipose tissue showed that, although IUGR affected pathways of substrate and energy metabolism in both males and females, important gender differences were evident. While IUGR males displayed alterations pointing to a predisposition to later development of obesity, the alterations observed in IUGR females pointed to a metabolic status of established obesity, in agreement with their increased fat pads mass.

Unraveling the role of high-intensity resistance training on left ventricle proteome: Is there a shift towards maladaptation?

High-intensity resistance training (RT) induces adaptations that improve physiological function. However, high intensity, volume and/or frequency may lead to injury and other health issues such as adverse cardiac effects. The aim of this study was to evaluate the effect of RT on left ventricle proteome, and to identify the pathways involved on the harmful adaptations induced by this protocol. Male Wistar rats were randomized into 2 groups: Trained (T) and Sedentary (S). Animals from T group were trained for 6weeks, and then all the animals were sacrificed and left ventricle was isolated for analysis. We identified 955 proteins, and 93 proteins were considered; 36 were expressed exclusively in T group, and 4 in S group. Based on quantitative analysis, 42 proteins were found overexpressed and 11 underexpressed in T group compared with S group. Using the Gene Ontology to relate the biological processes in which these proteins are involved, we conclude that RT protocol promotes changes similar to those found in the initial phase of heart failure, but we also observed a concomitant increased expression of protective proteins, suggesting the activation of pathways to avoid major damages on left ventricle and delay the onset of pathological hypertrophy. STATEMENT OF SIGNIFICANCE OF THE STUDY: Our study shows that high-intensity RT protocol changes left ventricle proteome, modifying metabolic profile of heart tissue and inducing the expression of proteins that acts against cardiac injury. We hypothesize that these adaptations occur to prevent the onset of cardiac dysfunction. Despite highly significant, it remains to be determined whether these adaptations are sufficient to further keep left ventricle function and exert cardioprotection, and whether this panel will be shifted towards maladaptation, and heart failure.

Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia.

Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated. Male rats received four daily injections of leptin (5 µg) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection. For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 µg) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (-74%) and the epididymal (-99%) depots while no differences were observed in the subcutaneous depot. The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected.