Hypothalamic AMP-activated protein kinase (AMPK) plays important roles in the regulation of food intake by altering the expression of orexigenic or anorexigenic neuropeptides. However, little is known about the mechanisms of this regulation. Here, we report that hypothalamic AMPK modulates the expression of NPY (neuropeptide Y), an orexigenic neuropeptide, and POMC (pro-opiomelanocortin-α), an anorexigenic neuropeptide, by regulating autophagic activity in vitro and in vivo. In hypothalamic cell lines subjected to low glucose availability such as 2-deoxy-d-glucose (2DG)-induced glucoprivation or glucose deprivation, autophagy was induced via the activation of AMPK, which regulates ULK1 and MTOR complex 1 followed by increased Npy and decreased Pomc expression. Pharmacological or genetic inhibition of autophagy diminished the effect of AMPK on neuropeptide expression in hypothalamic cell lines. Moreover, AMPK knockdown in the arcuate nucleus of the hypothalamus decreased autophagic activity and changed Npy and Pomc expression, leading to a reduction in food intake and body weight. AMPK knockdown abolished the orexigenic effects of intraperitoneal 2DG injection by decreasing autophagy and changing Npy and Pomc expression in mice fed a high-fat diet. We suggest that the induction of autophagy is a possible mechanism of AMPK-mediated regulation of neuropeptide expression and control of feeding in response to low glucose availability.
Background: Although the importance of gender as a key determinant in health and illness has been recognized for a long time, systematic studies of gender differences in medicine are still lacking. We hypothesized that interscapular brown adipocyte tissue (BAT), is not only a key tissue contributing to energy expenditure, but also regulates diet-induced thermogenesis, and may be an ideal target for studying gender differences in obesity development in response to a high fat diet (HFD). Methods: We therefore performed differential proteome analysis of BAT from lean and obese rats of both genders fed a HFD using 2-DE combined with MALDI-TOF-MS. Results: When exposed to a HFD, male rats gained more body weight with increased values of plasma biochemical parameters than did female rats. Among 595 matched spots, 48 differentially expressed identified spots showed significant gender differences, whereas 7 proteins showed no gender differences, but did show a HFD response. Conclusions: Proteomic investigations into gender-dimorphic protein modulation in BAT may provide conclusive results showing higher expression of numerous proteins involved in thermogenesis and fat oxidation as well as lower expression of proteins contributing to fat synthesis in female rats than in male rats.
This study evaluated the effects of blood contamination and decontamination methods during different steps of bonding procedures on the microtensile bond strength of two-step self-etch adhesives to dentin. Sixty extracted human molars were ground flat to expose occlusal dentin. The 60 molars were randomly assigned to three groups, each treated with a different two-step self-etch adhesive: Clearfil SE Bond, AdheSE and Tyrian SPE. In turn, these groups were subdivided into five subgroups (n = 20), each treated using different experimental conditions as follows: control group-no contamination; contamination group 1-CG1: primer application/ contamination/primer re-application; contamination group 2-CG2: primer application/contamination/wash/dry/primer re-application; contamination group 3-CG3: primer application/adhesive application/light curing/contamination/ adhesive re-application/light curing; contamina- tion group 4-CG4: primer application/adhesive application/light curing/contamination/wash/ dry/adhesive re-application/light curing. Composite buildup was performed using Z250. After 24 hours of storage in distilled water at 37 degrees C, the bonded specimens were trimmed to an hourglass shape and serially sectioned into slabs with 0.6 mm2 cross-sectional areas. Microtensile bond strengths (MTBS) were assessed for each specimen using a universal testing machine. The data were analyzed by two-way ANOVA followed by a post hoc LSD test. SEM evaluations of the fracture modes were also performed. The contaminated specimens showed lower bond strengths than specimens in the control group (p < 0.05), with the exception of CG1 in the Clearfil SE group and CG2 and CG3 in the Tyrian SPE group. Among the three self-etch adhesives, the Tyrian SPE group exhibited a significantly lower average MTBS compared to the Clearfil SE Bond and AdheSE (p < 0.05) groups. Based on the results of the current study, it was found that blood contamination reduced the MTBS of all three self-etch adhesives to dentin, and water-rinsing was unable to overcome the effects of blood contamination.
One of the major issues in the field of obesity is why some humans become obese and others resist development of obesity when exposed to high-calorie diets. Despite the same genetic background, namely obesity-prone (OP) and -resistant (OR) rats, differing responses have been demonstrated in a high fat diet-induced rodent model. The aim of the present study was to discover novel obesity-related biomarkers for susceptibility and/or resistance to obesity by proteomic analysis of OP and OR rat plasma. After feeding of high fat diet, OP rats gained approximately 25% more body weight than OR rats and were used for proteomic analysis using 2-DE combined with MALDI-TOF-MS. We categorized identified proteins into three groups by analysis of both average spot density in each group and individual spot density of six rats as a function of body weight. Consequently, category (1) included inter-α-inhibitor H4 heavy chain and fetuin B precursor, which can be used as novel plasma biomarkers for risk of obesity. Nine proteins of category (2) and (3) can also be plausible plasma markers in the study of obesity. This proteomic study is an important advancement over the previous steps needed for identification of OP and OR rats.
Background: Proper understanding of molecular mechanisms underlying gender dimorphism in obesity for better nutritional recommendation is still in early stages. As white adipose tissues (WAT) is most important tissue in obesity metabolism, comparative proteomic analysis of all three WAT deposits at the same time to yield immensely important protein markers was the primary goal of this study. Methods: We performed differential expression analysis of protein profiles of three different WAT viz. subcutaneous, inguinal, and abdominal fat deposits of both genders in lean and obese rats fed a high fat diet (HFD) using a combination of 2-DE and MALDI-TOF-MS. Results: The proteomics analysis enabled us to detect 25, 29, and 46 proteins showing gender differences in three WAT deposits, respectively, to gain insight into cause of higher body weight gain in male in response to HFD. Conclusion: The gender dimorphism found in this proteomic study implies that female rats have a lower tendency to undergo metabolic syndrome manifestation, which is associated with lower reliance on lipid as an energy fuel, lower lipogenesis, as well as increased mitochondrial oxidative capacity. In conclusion, most of the candidate proteins identified herein by differential proteomics were previously unrecognized in gender dimorphism of adipose tissue.
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