Brown adipose tissue in obesity: Fractalkine-receptor dependent immune cell recruitment affects metabolic-related gene expression.

Brown adipose tissue (BAT) plays essential role in metabolic- and thermoregulation and displays morphological and functional plasticity in response to environmental and metabolic challenges. BAT is a heterogeneous tissue containing adipocytes and various immune-related cells, however, their interaction in regulation of BAT function is not fully elucidated. Fractalkine is a chemokine synthesized by adipocytes, which recruits fractalkine receptor (CX3CR1)-expressing leukocytes into the adipose tissue. Using transgenic mice, in which the fractalkine receptor, Cx3cr1 gene was replaced by Gfp, we evaluated whether deficiency in fractalkine signaling affects BAT remodeling and function in high-fat-diet - induced obesity. Homo- and heterozygote male CX3CR1-GFP mice were fed with normal or fat enriched (FatED) diet for 10weeks. Interscapular BAT was collected for molecular biological analysis. Heterozygous animals in which fractalkine signaling remains intact, gain more weight during FatED than CX3CR1 deficient gfp/gfp homozygotes. FatED in controls resulted in macrophage recruitment to the BAT with increased expression of proinflammatory mediators (Il1a, b, Tnfa and Ccl2). Local BAT inflammation was accompanied by increased expression of lipogenic enzymes and resulted in BAT "whitening". By contrast, fractalkine receptor deficiency prevented accumulation of tissue macrophages, selectively attenuated the expression of Tnfa, Il1a and Ccl2, increased BAT expression of lipolytic enzymes (Atgl, Hsl and Mgtl) and upregulated genes involved thermo-metabolism (Ucp1, Pparg Pgc1a) in response to FatED. These results highlight the importance of fractalkine-CX3CR1 interaction in recruitment of macrophages into the BAT of obese mice which might contribute to local tissue inflammation, adipose tissue remodeling and regulation of metabolic-related genes

Baryon spectrum in the composite sextet model

The strongly coupled near-conformal gauge theory with two fermion flavors in the two-index symmetric (sextet) representation of SU(3) is potentially a minimal realization of the composite Higgs mechanism. We discuss the staggered fermion construction of baryonic states, present our first numerical results and comment on implications for dark matter

Toward the minimal realization of a light composite Higgs

Work in progress is reported on a particularly interesting gauge theory with a fermion doublet in the two-index symmetric (sextet) representation of the SU(3) color gauge group. Extending previous studies we outline our strategy as we investigate Goldstone dynamics and Electroweak scale setting from chiral symmetry breaking (χSB), test the GMOR relation from the spectrum of the Dirac operator and the related chiral condensate, begin to develop and test mixed action based improved analysis of χSB with new run plans at fixed topology to cross over from the p-regime to the epsilon-regime of χSB, continue to pursue the light 0++ scalar and its relation to the dilaton, and probe the scale-dependent running coupling from the perturbative UV scale to the scale of chiral symmetry breaking. Our observations suggest that the model is very close to the conformal window and a light composite scalar, perhaps the Higgs impostor with or without dilaton-like interpretation, appears to emerge with 0++ quantum numbers. The lightest baryon of the model on the 3 TeV scale has intriguing implications

Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling

Xenoestrogens from synthetic or natural origin represent an increasing risk of disrupted endocrine functions including the physiological activity of the hypothalamo-pituitary-gonad axis. Ethinyl estradiol (EE2) is a synthetic estrogen used in contraceptive pills, whereas zearalenone (ZEA) is a natural mycoestrogen found with increasing prevalence in various cereal crops. Both EE2 and ZEA are agonists of estrogen receptor alpha (ERalpha) and accelerate puberty. However, the neuroendocrine mechanisms that are responsible for this effect remain unknown. Immature female Wistar rats were treated with EE2 (10 mu g/kg), ZEA (10 mg/kg) or vehicle for 10 days starting from postnatal day 18. As a marker of puberty, vaginal opening was recorded and neuropeptide- and related transcription factor mRNA levels were measured by quantitative real time PCR and in situ hybridization histochemistry. Both ZEA and EE2 accelerated vaginal opening, increased uterine weight and the number of antral follicles in the ovary and resulted in increased central expression of gnrh. These changes occurred in parallel with an earlier increase of kiss1 mRNA in the anteroventral and rostral periventricular (AVPV/PeV) hypothalamus, and increased kisspeptin (KP) fiber density and KP-GnRH appositions in the preoptic area. These changes are compatible with a mechanism in which xenoestrogens overstimulate the developmentally unprepared reproductive system, which results in advanced vaginal opening and enlargement of the uterus at the periphery. Within the hypothalamus, ZEA and EE2 directly activate AVPV KP neurons to stimulate GnRH mRNA. However, GnRH and gonadotropin release and ovulation are disrupted due to xenoestrogen-mediated inhibitory KP signaling in the arcuate nucleus

Chiral properties of SU(3) sextet fermions

SU(3) gauge theory with overlap fermions in the 2-index symmetric (sextet) and fundamental representations is considered. A priori it is not known what the pattern of chiral symmetry breaking is in a higher dimensional representation although the general expectation is that if two representations are both complex, the breaking pattern will be the same. This expectation is verified for the sextet at N_f = 0 in several exact zero mode sectors. It is shown that if the volume is large enough the same random matrix ensemble describes both the sextet and fundamental Dirac eigenvalues. The number of zero modes for the sextet increases approximately 5-fold relative to the fundamental in accordance with the index theorem for small lattice spacing but zero modes which do not correspond to integer topological charge do exist at larger lattice spacings. The zero mode number dependence of the random matrix model predictions correctly match the simulations in each sector and each representation.Comment: 38 pages (12 pages text and gazillion tables/figures), minor modification, references adde

The metabolic stress response: Adaptation to acute-, repeated- and chronic challenges in mice

There is a strong relationship between stress and metabolism. Because acute traumatic- and chronic stress events are often accompanied with metabolic pathophysiology, it is important to understand the details of the metabolic stress response. In this study we directly compared metabolic effects of acute stress with chronic repeated- and chronic unpredictable stress in mouse models. All types of adversities increased energy expenditure, chronic stress exposure decreased body weight gain, locomotor activity and differentially affected fuel utilization. During chronic exposure to variable stressors, carbohydrates were the predominant fuels, whereas fatty acids were catabolized in acutely and repeatedly restrained animals. Chronic exposure to variable stressors in unpredictable manner provoked anxiety. Our data highlight differences in metabolic responses to acute- repeated- and chronic stressors, which might affect coping behavior and underlie stress-induced metabolic and psychopathologies. © 202