Endocrinology
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Osteocalcin, a synthetic osteoblast-specific protein, has recently emerged as an important regulator of energy metabolism, but the underlying mechanisms are not fully understood. In the present study, mice fed a high-fat diet and receiving osteocalcin showed reduced body weight gain, less fat pad gain, and improved insulin sensitivity as well as increased energy expenditure compared with mice fed a high-fat diet and receiving vehicle. Meanwhile, increased endoplasmic reticulum (ER) stress, defective insulin signaling, and mitochondrial dysfunction induced by obesity were also effectively alleviated by treatment with osteocalcin. ⋯ These effects were nullified by blockade of nuclear factor-κB (NF-κB) or phosphatidylinositol 3-kinase but not by U0126, a mitogen-activated protein kinase inhibitor, indicating the causative role of phosphatidylinositol 3-kinase/NF-κB in action of osteocalcin. In addition, the reversal effects of osteocalcin in cells deficient in X-box-binding protein-1, a transcription factor that modulates ER stress response, further confirmed its protective role against ER stress and insulin resistance. Our findings suggest that osteocalcin attenuates ER stress and rescues impaired insulin sensitivity in insulin resistance via the NF-κB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.
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Mounting evidence has established hydrogen sulfide (H(2)S) as an important gasotransmitter with multifaceted physiological functions. The aim of the present study was to investigate the role of H(2)S on glucose utilization, glycogen synthesis, as well as gluconeogenesis in both HepG(2) cells and primary mouse hepatocytes. Incubation with NaHS (a H(2)S donor) impaired glucose uptake and glycogen storage in HepG(2) cells via decreasing glucokinase activity. ⋯ In addition, insulin at the physiological range inhibited CSE expression, and H(2)S decreased insulin-stimulated phosphorylation of Akt in HepG(2) cells. CSE expression was increased, however, in insulin-resistant state induced by exposing cells to high levels of insulin (500 nm) and glucose (33 mm) for 24 h. Taken together, these data suggest that the interaction of H(2)S and insulin in liver plays a pivotal role in regulating insulin sensitivity and glucose metabolism.
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The kisspeptin system has emerged as one of the most important circuits within the central network governing reproduction. Although kisspeptin physiology has been examined in many species, much of our understanding of this system has come from mice. Recently, the study of several innovative strains of genetically engineered mouse models has revealed intriguing and unexpected insights into the functions of kisspeptin signaling in the hypothalamus. Here, we review the advancements in our knowledge of the central kisspeptin system through the use of mutant mice.
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Males and females have the same immunological cells, proteins, and pathways in place to protect against the development of disease. The kinetics, magnitude, and skewing of the responses mounted against pathogens, allergens, toxins, or self-antigens, however, can differ dramatically between the sexes. Generally, females mount higher innate and adaptive immune responses than males, which can result in faster clearance of pathogens but also contributes to increased susceptibility to inflammatory and autoimmune diseases in females compared with males. ⋯ In particular, the expression of X-linked genes and microRNA as well as sex steroid hormones signaling through hormone receptors in immune cells can affect responses to immunological stimuli differently in males and females. Despite data illustrating profound differences between the sexes in immune function, sex differences in the pathogenesis of disease are often overlooked in biomedical research. Establishing journal policies that require authors to report the sex of their cells, animals, and subjects will improve our understanding of the pathogenesis of diseases, with the long-term goal of personalizing treatments for immune-mediated diseases differently for males and females in an effort to protect us equally.