Adipose tissue (AT) is a highly heterogeneous and dynamic organ that plays important roles in regulating energy metabolism and insulin sensitivity. In addition to its classical roles in nutrient ...sensing and energy storage/dissipation, AT secretes a large number of bioactive molecules (termed adipokines) participating in immune responses and metabolic regulation through their paracrine and/or endocrine actions. Adipose-derived extracellular vesicles (ADEVs), including exosomes, microvesicles (MVs), and apoptotic bodies, have recently emerged as a novel class of signal messengers, mediating intercellular communications and inter-organ crosstalk. In AT, ADEVs derived from adipocytes, immune cells, mesenchymal stem cells, endothelial cells are actively involved in modulation of immune microenvironment, adipogenesis, browing of white adipose tissue, adipokine release and tissue remodeling. Furthermore, ADEVs exert their metabolic actions in distal organs (such as liver, skeletal muscle, pancreas and brain) by sending genetic information (mainly in the form of microRNAs) to their target cells for regulation of gene expression. Here, we provide an updated summary on the nature and composition of ADEVs, and their pathophysiological functions in regulating immune responses, whole-body insulin sensitivity and metabolism. Furthermore, we highlight the latest clinical evidence supporting aberrant production and/or function of ADEVs as a contributor to obesity-related chronic inflammation and metabolic complications and discuss the opportunities and challenges in developing novel therapies by targeting ADEVs.
In this paper two kinds of identities involving derangement polynomials and $ r $-Bell polynomials were established. The identities of the first kind extended the identity on derangement numbers and ...Bell numbers due to Clarke and Sved and its generalizations due to Du and Fonseca. The identities of the second kind extended some of the results on derangement polynomials and Bell polynomials due to Kim et al.
Fibroblast growth factor 21 (FGF21) is a stress-inducible hormone that has important roles in regulating energy balance and glucose and lipid homeostasis through a heterodimeric receptor complex ...comprising FGF receptor 1 (FGFR1) and β-klotho. Administration of FGF21 to rodents or non-human primates causes considerable pharmacological benefits on a cluster of obesity-related metabolic complications, including a reduction in fat mass and alleviation of hyperglycaemia, insulin resistance, dyslipidaemia, cardiovascular disorders and non-alcoholic steatohepatitis (NASH). However, native FGF21 is unsuitable for clinical use owing to poor pharmacokinetic and biophysical properties. A large number of long-acting FGF21 analogues and agonistic monoclonal antibodies for the FGFR1-β-klotho receptor complexes have been developed. Several FGF21 analogues and mimetics have progressed to early phases of clinical trials in patients with obesity, type 2 diabetes mellitus and NASH. In these trials, the primary end points of glycaemic control have not been met, whereas substantial improvements were observed in dyslipidaemia, hepatic fat fractions and serum markers of liver fibrosis in patients with NASH. The complexity and divergence in pharmacology and pathophysiology of FGF21, interspecies variations in FGF21 biology, the possible existence of obesity-related FGF21 resistance and endogenous FGF21 inactivation enzymes represent major obstacles to clinical implementation of FGF21-based pharmacotherapies for metabolic diseases.
In this paper, we provide an estimate for approximating the generalized-Euler-constant function
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. We ...obtain an asymptotic expansion for the generalized-Euler-constant function and show that the coefficients of the asymptotic expansion are explicitly expressed by the Eulerian fractions. Also, we find a recurrence relation for those coefficients. Using its relation with the generalized-Euler-constant function, we establish two inequalities for the generalized Somos’ quadratic recurrence constant. Moreover, two asymptotic expansions for the natural logarithm of the generalized Somos quadratic recurrence constant are presented.
Persistent, unresolved inflammation in adipose tissue is a major contributor to obesity-associated metabolic complications. However, the molecular links between lipid-overloaded adipocytes and ...inflammatory immune cells in obese adipose tissues remain elusive. Here we identified adipocyte-secreted microRNA-34a (miR-34a) as a key mediator through its paracrine actions on adipose-resident macrophages. The expression of miR-34a in adipose tissues was progressively increased with the development of dietary obesity. Adipose-selective or adipocyte-specific miR-34a-KO mice were resistant to obesity-induced glucose intolerance, insulin resistance, and systemic inflammation, and this was accompanied by a significant shift in polarization of adipose-resident macrophages from proinflammatory M1 to antiinflammatory M2 phenotype. Mechanistically, mature adipocyte-secreted exosomes transported miR-34a into macrophages, thereby suppressing M2 polarization by repressing the expression of Krüppel-like factor 4 (Klf4). The suppressive effects of miR-34a on M2 polarization and its stimulation of inflammatory responses were reversed by ectopic expression of Klf4 in both bone marrow-derived macrophages and adipose depots of obese mice. Furthermore, increased miR-34a expression in visceral fat of overweight/obese subjects correlated negatively with reduced Klf4 expression, but positively with the parameters of insulin resistance and metabolic inflammation. In summary, miR-34a was a key component of adipocyte-secreted exosomal vesicles that transmitted the signal of nutrient overload to the adipose-resident macrophages for exacerbation of obesity-induced systemic inflammation and metabolic dysregulation.
There is a close anatomical and functional relationship between adipose tissue and blood vessels. The crosstalk between these two organs is vital to both metabolic and vascular homeostasis. On the ...one hand, adipose tissue is highly vascularized, and maintenance of ample supply of blood flow is essential for both expansion and metabolic functions of adipose tissue. Vascular endothelium also secretes many factors to regulate adipogenesis and adipose tissue remodeling. On the other hand, almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which regulates vascular function by producing a large number of “vasocrine” molecules. Under the normal conditions, PVAT exerts its anti-contractile effects by release of vasorelaxants (such as adipocyte-derived relaxation factors and adiponectin) that promote both endothelium-dependent and –independent relaxations of blood vessels. However, PVAT in obesity becomes highly inflamed and induces vascular dysfunction by augmented secretion of vasoconstriction factors (such as the major components of renin-angiotensinogen-aldosterone system and superoxide) and pro-inflammatory adipokines (such as TNF-α and adipocyte fatty acid binding protein), the latter of which are important contributors to endothelial activation, vascular inflammation and neointimal formation. Furthermore, several adipocyte-derived adipokines impair vascular function indirectly, by acting in the brain to activate sympathetic nerve system (such as leptin) or by exerting their actions in major metabolic organs to induce vascular insulin resistance, which in turn aggravates endothelial dysfunction. Aberrant secretion of adipokines and other vasoactive factors in adipose tissue is a major contributor to the onset and progression of obesity-related metabolic and vascular complications.
Alkali activated binders (geopolymer) is an emerging technology to produce concrete without the use of any Ordinary Portland Cement (OPC) by alkali activation of alumino-silicate source materials ...such as fly ash and/or slag. Limited knowledge on durability issues like corrosion behaviour of reinforced geopolymer concrete impedes the usage of this technology in structural applications.
This study explored the chloride permeability and initiation of chloride induced corrosion of geopolymer concrete in accelerated chloride environment using longer test period. Corrosion initiation was also monitored in embedded rebar in 2% chloride contaminated concrete. Corrosion state of the rebar was monitored using non-destructive test method using Cu/CuSO4 reference electrode.
The results showed that the apparent chloride diffusion coefficient of blended fly ash and slag geopolymer concrete is lower than that of OPC concrete. The diffusion coefficient also decreased with the increase of slag content in the binder. Blended fly ash and slag geopolymer concrete also exhibited higher aging factor than OPC concrete indicating improved resistance to chloride ingress with time. The study also showed that the embedded rebar in fly ash and slag based geopolymer concrete has higher protection against corrosion than a rebar in OPC concrete even when the concrete is contaminated with significant levels of chloride.
•Chloride ingress rate in geopolymers containing slag is low.•Age factor of geopolymer is significantly higher than OPC.•Geopolymer can hinder corrosion in steel rebar.
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Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in ...39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity (clinicaltrials.gov entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.
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•A high variability in glycemic response to exercise in subjects with prediabetes exists•Responders and non-responders exhibit differential alterations of the gut microbiota•Gut microbiota from responders confers the metabolic benefits of exercise in mice•Baseline microbiome features accurately predict personalized exercise responses
Liu et al. identify the gut microbiota as an important determinant in the responsiveness of individuals with prediabetes to exercise for the improvement of glucose metabolism and insulin sensitivity. These findings may help in the implementation of a personalized lifestyle intervention for diabetes prevention.
Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent ...differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
Abstract
Adipose tissue (AT) is highly plastic and heterogeneous in response to environmental and nutritional changes. The development of heat-dissipating beige adipocytes in white AT (WAT) through a ...process known as browning (or beiging) has garnered much attention as a promising therapeutic strategy for obesity and its related metabolic complications. This is due to its inducibility in response to thermogenic stimulation and its association with improved metabolic health. WAT consists of adipocytes, nerves, vascular endothelial cells, various types of immune cells, adipocyte progenitor cells, and fibroblasts. These cells contribute to the formation of beige adipocytes through the release of protein factors that significantly influence browning capacity. In addition, inter-organ crosstalk is also important for beige adipocyte biogenesis. Here, we summarize recent findings on fat depot-specific differences, secretory factors participating in intercellular and inter-organ communications that regulate the recruitment of thermogenic beige adipocytes, as well as challenges in targeting beige adipocytes as a potential anti-obese therapy.
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