The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum-fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype

Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine) and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs). In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the neurohormonal mechanisms involved in the beneficial effects of KDs. In this review, we summarize the current evidence for altered regulation of the synthesis of neuropeptides and peripheral hormones in response to KDs, and we try to define a possible role for specific neuroactive peptides in mediating the antiepileptic properties of diet-induced ketogenesis

Stress-induced thermoelastic martensitic transformations and functional properties in [011]-oriented NiTiHfPd single crystals

The stress-induced martensitic transformation in the [011]-oriented Ni45.3Ti29.7Hf20Pd5 (at. %) single crystals in as-grown, homogenized and aged states were investigated in compression. It is experimentally shown that heat treatments of single crystals result in increase in martensitic transformation temperatures, two-fold decrease in reversible strain and increase in strain-hardening coefficient. As-grown single crystals demonstrate large temperature range of superelasticity (up to 140 K), large reversible strain (up to 4.3%) and large work output in comparison with homogenized and aged crystals

The effect of subsequent stress‐induced martensite aging on the viscoelastic properties of aged NiTiHf polycrystals

This study investigated the effect of stress‐induced martensite aging under tensile and compressive stresses on the functional and viscoelastic properties in Ni50.3Ti32.2Hf17.5 polycrystals containing dispersed H‐phase particles up to 70 nm in size obtained by preliminary austenite aging at 873 K for 3 h. It was found that stress‐induced martensite aging at 428 K for 12 h results in the appearance of a two‐way shape memory effect of −0.5% in compression and +1.8% in tension. Moreover, a significant change in viscoelastic properties can be observed: an increase in internal friction (by 25%) and a change in elastic modulus in tensile samples. The increase in internal friction during martensitic transformation after stress‐induced martensite aging is associated with the oriented growth of thermal‐induced martensite. After stress‐induced martensite aging, the elastic modulus of martensite (EM) increased by 8 GPa, and the elastic modulus of austenite (EA) decreased by 8 GPa. It was shown that stress‐induced martensite aging strongly affects the functional and viscoelastic properties of material and can be used to control them

The cyclic stability of rubber-like behaviour in stress-induced martensite aged Ni49Fe18Ga27Co6 (at.%) single crystals

In present work, the cyclic stability of the rubber-like behaviour (RLB) was investigated in Ni49Fe18Ga27Co6 (at. %) single crystals. Crystals were aged in the martensite phase at 423 K for 1 h under a compressive stress of 450 MPa, applied along the [110]B2[100]L10-direction. The RLB was induced by a preliminary chemical stabilization of the oriented L10-martensite during stress-induced martensite aging (SIM-aging) and following the reversible reorientation of martensitic variants under a compressive stress applied along the [001]B2[001]L10-direction. The high cyclic stability of the RLB was obtained in 200 loading/unloading cycles, due to the low reorientation stresses of the L10-martensite variants (no higher than 140 MPa) and the high strength properties of the L10-martensite (~1.6 GPa). The irreversible strain after 200 cycles did not exceed 0.6%. An increase in the number of cycles did not lead to the effect of destabilization of the L10-martensite

The Particles “ga and “no in Sonezaki-Shinju: Changes in the Usages of the particle “ga

本稿では、大野(1987)のデータに『曽根崎心中』のデータを加え、助詞「が」の用法の変遷について観察した。その結果、『土佐日記』以来「が」の使用比率は「の」と比較すると若干の増減をみせながらも、全体として増加傾向にあるといえ『曽根崎心中』も、その変化過程の中にあることを明らかにした(図2・図3)。また「が」のかかる形式比率(図4)でも「体言が体言」から「体言が用言」へ移行する変化の中にあることが明らかになった。『曽根崎心中』では助詞「が」の連体・主格・接続といった3つの用法が認められる。その中でもまず、主格用法が「が」の全用例の52パーセントを占め、最も用例の多い用法であった。次に連体用法の「が」についていえば、基本的にはウチ・ソトの区別で「が」の承ける体言が決定されているが、「二人の心ぞ」「二人が中に降る涙」のように「二人」という体言を「が」と「の」の両助詞で承けており、ウチ・ソト意識の混乱が見られる

The effect of stress-induced martensite aging in tension and compression on B2–B19′ martensitic transformation in Ni50.3Ti32.2Hf17.5 high-temperature shape memory alloy

The present study investigates the high-temperature shape memory effect (SME) in heterophase Ni50.3Ti32.2Hf17.5 polycrystals with nanosized H-phase particles after stress-induced martensite (SIM) aging in tension and compression. SIM aging created the conditions for fully reversible two-way SME with a strain of up to 50% of the one-way shape memory strain. SIM aging altered the viscoelastic properties of material, in particular, the elastic moduli of austenite and martensite increased, as did internal friction. Increased interface mobility is suggested as the reason for internal friction growth

Orientation dependence of superelasticity in quenched high-nickel Ti51.8Ni single crystals

The orientation dependence of the functional and mechanical properties of quenched Ti-51.8at.%Ni single crystals, undergoing a strain-glass transition upon cooling/heating was investigated. It was found that a compressive stress above 800 MPa leads to the B2-B190 martensitic transformation (MT), regardless of orientation. In the high-strength [0 0 1]-orientation, superelasticity (SE) was observed at 203–248 K, with a reversible strain of 2.3%. Degradation of SE at deforming stresses r > 1000 MPa was associated with the formation of {1 1 3}B2 twins during the reverse MT. In the low-strength 1 1 1-orientation, the formation of stress-induced B190 -martensite occurred simultaneously with the plastic deformation of the B2-phase (due to the formation of reorientation bands and dislocation slip) and a reversible strain was not observed