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The hypothalamus is a crucial brain region that mediates the effects of insulin and leptin signals on peripheral metabolic functions. Previous research has shown that insulin signals in the hypothalamus act via multiple neuronal circuits and anabolic/catabolic pathways that converge on the vagus nerve and sympathetic fibers to coordinate energy metabolism in peripheral organs. Additionally, neuropeptide FF (NPFF) has been identified as a regulator of feeding behaviors and energy homeostasis in the hypothalamus, but the mechanisms underlying its involvement in metabolic control remain unclear. This study aims to explore the underlying mechanisms of NPFF in modulating metabolic disorders. In this study, we investigated the physiological role of NPFF in insulin-related energy homeostasis and metabolic health. First, we evaluated the effects of NPFF and its receptors on central insulin signaling using mouse hypothalamic cell lines and Npffr2 -overexpressing mice. To further explore the effects of NPFFR2 on insulin-related metabolic disorders, such as diabetes mellitus, we used Npffr2 -deleted mice in combination with the streptozotocin (STZ)-induced type 1 diabetes and high-fat diet/STZ-induced type 2 diabetic mouse models. The impacts of central NPFFR2 were demonstrated specifically through Npffr2 overexpression in the hypothalamic arcuate nucleus, which subsequently induced type 2 diabetes. We found that stimulating NPFFR2 in the hypothalamus blocked hypothalamic insulin activity. Npffr2 deletion improved central and peripheral metabolic symptoms in both mouse models of diabetes mellitus, exerting effects on central and systemic insulin resistance, feeding behaviors, glucose and insulin intolerance, lipid metabolism, liver steatosis, and inflammation of white adipose tissues. The overexpression of ARC Npffr2 augmented the metabolic dysregulation in the mouse model of type 2 diabetes. Our findings demonstrate that hypothalamic NPFFR2 negatively regulates insulin signaling in the central nervous system and plays an important role in maintaining systemic metabolic health, thereby providing valuable insights for potential clinical interventions targeting these health challenges. [Display omitted] [ABSTRACT FROM AUTHOR]

A dynamic material model is presented to characterize the mechanical behavior of rock materials under high confining pressures and high strain rates. The yield surface is defined based on the extended Drucker–Prager strength criterion and the Johnson–Cook material model. Two internal damage variables are introduced to represent, respectively, the tensile and compressive damage of rock materials. The proposed dynamic material model of rocks is incorporated into the nonlinear dynamic analysis code LS-DYNA through a user-defined material interface. Its reliability and accuracy are verified by the simulation of various basic experiments with different loading conditions. The present rock model is also applied to simulate the penetration of granite target plate by hard projectile. The typical damage and failure on the granite targets predicated by the proposed dynamic material model of rocks agree well with the experimental results. It demonstrates that the proposed model is capable of capturing the failure of rock materials. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relationship between temporal and spatial expression patterns of Fos protein in the spinal dorsal horn neurons and thermal hyperalgesia behaviors in rats with chronic constriction injury (CCI) to the sciatic nerve. Our results demonstrated that Fos protein expression in the spinal dorsal horn neurons at L5 segment ipsilateral and contralateral to CCI of the sciatic nerve was significantly greater than in sham rats from days 10 to 30 postoperatively (PO 10d to 30d), and was concentrated on the injury (ipsilateral) side. Unlike the short-lived expression after tissue inflammation, laminae I to VI (especially laminae III/IV) displayed a persistent greater number of Fos-like immunoreactive (Fos-LI) neurons for at least 30 days after CCI of the sciatic nerve. After the increase in laminae III/IV, Fos-LI neurons tended to gradually increase in laminae I/II and V/VI at L5 segment from PO 2d to 30d, which were correlated with the heat hyperalgesia (48 °C) behaviors measured by paw withdrawal latency in CCI rats but not in sham rats. Interestingly, a persistent increase of Fos-LI neurons in laminae I to VI at L5 segment of the ipsilateral and contralateral sides and at the L1 segment that was out of the normal central terminations of the sciatic nerve suggested the probable presence of territorial and extra-territorial central sensitization or inadequate central nervous system (CNS) adaptive mechanisms. These findings may partly explain why abnormal pain sensations are sometimes distributed in a pattern that does not coincide with the territories of nerves or with the posterior roots of the peripheral nerve after injury. [Copyright &y& Elsevier]

Anatomical relationships of hypothalamic cocaine- and amphetamine-regulated transcript (CART) with other hypothalamic neuropeptides were examined by using in situ hybridization histochemistry and immunohistochemistry. CART mRNA was found in various regions in rat hypothalamus, including the periventricular nucleus, paraventricular nucleus, dorsomedial nucleus, perifornical regions, lateral nucleus, and the arcuate nucleus. In the paraventricular nucleus, CART mRNA is colocalized with vasopressin and corticotropin-releasing factor-containing neurons. Moreover, either fasting or diabetes attenuates CART mRNA expression in the hypothalamus, demonstrating that CART mRNA regulation is related to the fuel availability and peripheral hormonal status. Our findings suggest that the presence of CART mRNA in specific cell groups of the hypothalamus plays a role in hypothalamic regulation of neuroendocrine functions. [Copyright &y& Elsevier]

The effects of cocaine-and amphetamine-regulated transcript (CART) peptide on extracellular concentrations of dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the shell region of the nucleus accumbens (AcbSh) were determined by microdialysis in conscious rats. Intracerebroventricular injections of various doses (0.1–5 μg/5 μl/rat) of CART55–102 elicited dose-dependent increases of extracellular DOPAC and HVA concentration in the AcbSh, suggesting that CART55–102 peptide has a psychostimulant-like effect via activation of the mesolimbic dopaminergic system. [Copyright &y& Elsevier]