Release Of Adipokines Research Articles

Abstract 15842: Body Mass Index in Covid-19: An Independent Risk Factor for Severe Infections

Introduction: The coronavirus disease 2019 (COVID-19) led to a global pandemic. Comorbidities such as hypertension, diabetes mellitus, elevated cholesterol, cardiac/pulmonary diseases, and obesity were postulated as prognostic factors for a worse outcome. Hypothesis: Obese COVID-19 patients have a worse prognosis. Methods: From March to June 2020, we obtained data on all patients ≥18 y.o. who were admitted with a positive COVID-19 test at the Rush System, Chicago. Multivariable logistic regression analysis was performed between predictors and a composite outcome of intubation and in-hospital mortality. Results: Among the 1345 admitted patients, 69 (5%) were underweight (BMI<18.5kg/m2), 365 (27%) of normal weight (BMI 18.5-25kg/m2), 405 (30%) overweight (BMI 25-30kg/m2), 258 (19%) of obesity class I (BMI 30-35kg/m2), 119 (9%) of obesity class II (BMI 35-40kg/m2) and 129 (10%) of obesity class III (BMI >40kg/m2). In a multivariable model assessing the risk for the in-hospital death or intubation, underweight patients showed decreased risk (odds ratio (OR) 0.31) while obesity class III patients showed increased risk (OR 1.68, Figure 1) when compared to normal BMI. When accounting for obesity classes, male sex, atrial fibrillation and coronary artery disease were also independent predictors adverse outcomes. Conclusions: Consistent with previous research, morbidly obese patients had a higher risk for a worse outcome, even when accounting for numerous comorbidities. Underweight patients appeared to be protected. Higher body mass leads to inherent changes in lung function, increased risk of thrombosis, greater viral replication, higher release of adipokines and higher inflammation. Inversely, fewer adipocytes could possibly limit the risk for cytokine storm by reducing the amount of proinflammatory factors released. Figure: Odds ratios with 95% confidence intervals for the outcome of death or intubation in all COVID-19 positive admitted patients.

Impact of Obesity-Related Inflammation on Cardiac Metabolism and Function.

This review focuses on the role of adipose tissue in obese individuals in the development of metabolic diseases, and their consequences for metabolic and functional derangements in the heart. The general idea is that the expansion of adipocytes during the development of obesity gives rise to unhealthy adipose tissue, characterized by low-grade inflammation and the release of proinflammatory adipokines and fatty acids (FAs). This condition, in turn, causes systemic inflammation and elevated FA concentrations in the circulation, which links obesity to several pathologies, including impaired insulin signaling in cardiac muscle and a subsequent shift in myocardial substrate oxidation in favor of FAs and reduced cardiac efficiency. This review also argues that efforts to prevent obesity-related cardiometabolic disease should focus on anti-obesogenic strategies to restore normal adipose tissue metabolism.

Adipokines and Inflammation: Focus on Cardiovascular Diseases.

It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.

Characterization and Treatment of Inflammation and Insulin Resistance in Obese Adipose Tissue.

Adipose tissue is the largest energy storage and protection organ. It is distributed subcutaneously and around the internal organs. It regulates metabolism by storing and releasing fatty acids and secreting adipokines. Excessive nutritional intake results in adipocyte hypertrophy and proliferation, leading to local hypoxia in adipose tissue and changes in the release of adipokines. These lead to recruit of more immune cells into adipose tissue and release of inflammatory signaling factors. Excess free fatty acids and inflammatory factors interfere with intracellular insulin signaling. In this review, we summarize the characteristics of obese adipose tissue and analyze how its inflammation causes insulin resistance. We further discuss the latest clinical research progress on the control of insulin resistance and inflammation resulting from obesity through anti-inflammatory therapy and bariatric surgery. Our review shows that targeted anti-inflammatory therapy is of great significance for obese patients with insulin resistance.

Intricacies of the endothelin system in human obesity: role in the development of complications and potential as a therapeutic target.

Activation of the vascular endothelin-1 (ET-1) system is a key abnormality in vascular dysfunction of human obesity, especially in patients developing complications, such as the metabolic syndrome, diabetes, and atherosclerosis. Vascular insulin resistance, an increased insulin-stimulated endothelial production of ET-1 combined with impaired nitric oxide availability, is the hallmark of obesity-related vasculopathy, but dysregulated adipokine release from obese adipose tissue may contribute to the predominance of ET-1-dependent vasoconstriction. ET-1, in turn, might determine unhealthy obese adipose tissue expansion, with visceral and perivascular adipose tissue changes driving the release of inflammatory cytokines and atherogenic chemokines. In addition, ET-1 might also play a role in the development of the metabolic complications of obesity. Studies have shown inhibition of lipoprotein lipase activity by ET-1, with consequent hypertriglyceridemia. Also, ET-1 in pancreatic islets seems to contribute to beta cell dysfunction, hence affecting insulin production and development of diabetes. Moreover, ET-1 may play a role in nonalcoholic steatohepatitis. Recent clinical trials using innovative design have demonstrated that antagonism of ET-type A receptors protects against some complications of obesity and diabetes, such as nephropathy. These findings encourage further investigation to evaluate whether targeting the ET-1 system could afford better protection against other consequences of the obesity epidemic.

Mismatch of Glucose Allocation between Different Life Functions in the Transition Period of Dairy Cows.

Simple SummaryThe reasons for the development of diseases in the transition period of dairy cows are manifold and highly farm- and cow-specific. Nevertheless, links exist between the degree of negative energy balance (NEB) and disease susceptibility, which suggest a mutual adverse relationship between immune and productive functions. Glucose is the most essential fuel and precursor for both immune cells and mammary epithelial cells (MEC). While the delivery of glucose by the intermediary metabolism is not always able to keep up with whole-body demands, trade-offs between mammary and immune cells emerge. The prioritization of mammary supply during early lactation is a physiologic principle in all mammals. In contrast, tremendous increases in milk yield and the specific demand for glucose in high-yielding dairy cows resulting from decades of selection for milk production override the evolutionary principles of nutrient partitioning. Therefore, high-producing dairy cows face an increased risk of glucose shortages in their immune cells, particularly during early lactation.Immune cell functions such as phagocytosis and synthesis of immunometabolites, as well as immune cell survival, proliferation and differentiation, largely depend on an adequate availability of glucose by immune cells. During inflammation, the glucose demands of the immune system may increase to amounts similar to those required for high milk yields. Similar metabolic pathways are involved in the adaptation to both lactation and inflammation, including changes in the somatotropic axis and glucocorticoid response, as well as adipokine and cytokine release. They affect (i) cell growth, proliferation and activation, which determines the metabolic activity and thus the glucose demand of the respective cells; (ii) the overall availability of glucose through intake, mobilization and gluconeogenesis; and (iii) glucose uptake and utilization by different tissues. Metabolic adaptation to inflammation and milk synthesis is interconnected. An increased demand of one life function has an impact on the supply and utilization of glucose by competing life functions, including glucose receptor expression, blood flow and oxidation characteristics. In cows with high genetic merits for milk production, changes in the somatotropic axis affecting carbohydrate and lipid metabolism as well as immune functions are profound. The ability to cut down milk synthesis during periods when whole-body demand exceeds the supply is limited. Excessive mobilization and allocation of glucose to the mammary gland are likely to contribute considerably to peripartal immune dysfunction.

The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model.

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

Fatigue in patients with plaque-type psoriasis: lack of an association with plasma cytokines.

Fatigue is common in patients with psoriasis, and cytokines have been postulated to influence fatigue. This case-control study explored the plasma levels of selected cytokines in patients with psoriasis and compared them with fatigue and other clinical factors. Eighty-four patients with chronic plaque-type psoriasis and 84 age- and gender-matched healthy subjects were enrolled. Psoriasis severity was measured using the Psoriasis Area and Severity Index (PASI), and skin-related quality of life using the Dermatology Life Quality Index (DLQI). Fatigue was rated with the fatigue Visual Analogue Scale (fVAS). Plasma levels of interleukin (IL)-1β, IL-1Rα, IL-1RII, IL-6, and IL-10 were measured by electrochemiluminescence sandwich immunoassay and ELISA. IL-1Rα and IL-6 median concentrations were significantly higher in patients than healthy subjects: 203pg/mL (interquartile range: 150-274) versus 166pg/mL (128-212), p=0.008 for IL-Rα, and 0.82pg/mL (0.25-1.40) versus 0.50pg/mL (0.25-0.91), p=0.009 for IL-6. IL-1β, IL-1RII, and IL-10 concentrations did not differ between patients and healthy subjects. Higher levels of IL-1Rα and IL-6 were associated with increased body mass index (BMI), but not with disease activity. Cytokine concentrations were not associated with fatigue. These findings do not support an association between fatigue and blood concentrations of selected pro- and anti-inflammatory cytokines. The increased IL-1Rα and IL-6 levels associated with increased BMI are probably caused by release of adipokines from adipose tissue; of these, leptin, in particular, is known to be a strong inflammatory stimulator.

Проблема остеоартроза (ОА) коленного сустава у пациентов с избыточной массой тела и ожирением: вопросы этиологии и патогенеза (обзор литературы)

Introduction Based on WHO report, in 2008, the global prevalence of overweight reached over 1.4 billion people aged 20 years and over including more than 200 million men and 300 million women who suffered from obesity in 2012. More than 34 % of U.S. adults are overweight, and more than 27 % are obese. In European countries, the prevalence of obesity is 35–40 % among adult population. More than 30 percent of the Russia’s working population is overweight, 25 percent of whom are obese. Material and methods Search engines used included MEDLINE, the primary component of Pubmed; the Electronic Library System, products from Elsevier and Springer publishing companies; open access articles of PubMed Central; BioMed Central; Free Medical Journals and open access publications using the keywords 'knee osteoarthritis', 'etiology and pathogenesis', 'knee osteoarthritis in obesity'. Results and discussion Osteoarthritis (OA) is multifactorial in origin and closely associated with genetic predisposition, sex and age, greater body mass index (BMI) and obesity. Family history, age, gender, previous injury or abnormal mechanical loading are common risk factors of knee OA. While the above risk factors can increase the chances of developing knee OA, they are not absolute. In clinical practice, in patients with new onset of knee pain 5.1 % of cases are due to previous knee injury and 24.6 % related to being overweight or obese. Such metabolic factors as obesity and dyslipidemia might be involved in the pathophysiology of knee OA. Increased free radical production associated with obesity results in degradation of articular cartilage and synovial involvement. The pathogenesis of knee OA attributable to obesity is predominantly related to unfavorable mechanical environment at the joint; chronic inflammation in adipose tissue and dyslipidemia; pro-inflammatory cytokines and adipokines secreted by the adipose tissue; cytokines secreted by infrapatellar fat pad. Conclusion Inflammatory mediators of adipose origin play a major role in the initiation and perpetuation of the obesity-induced OA. There is a significant multifactorial association between OA and obesity with central roles for LDL oxyforms, HDL synthesis and excessive activation of matrix metalloproteinases, adiponectin synthesis, the release of adipokines and excessive mechanical stress.

Sirtuin-1 and Its Relevance in Vascular Calcification.

Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of β-catenin that, following the facilitation of β-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.

Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease

Adipose tissue and the liver play significant roles in the regulation of whole-body energy homeostasis, but they have not evolved to cope with the continuous, chronic, nutrient surplus seen in obesity. In this review, we detail how prolonged metabolic stress leads to adipose tissue dysfunction, inflammation, and adipokine release that results in increased lipid flux to the liver. Overall, the upshot of hepatic fat accumulation alongside an insulin-resistant state is that hepatic lipid enzymatic pathways are modulated and overwhelmed, resulting in the selective buildup of toxic lipid species, which worsens the pro-inflammatory and pro-fibrotic shift observed in nonalcoholic steatohepatitis.

Through fat and thin - a journey with the adipose tissues.

The paper is based on the lecture that I gave on receiving the Nutrition Society's inaugural Gowland Hopkins Award for contributions to Cellular and Molecular Nutrition. It reviews studies on the adipose tissues, brown and white, conducted by the groups that I have led since entering nutrition research in 1975. The initial focus was on exploring metabolic factors that underpin the development of obesity using animal models. This resulted in an interest in non-shivering thermogenesis with brown adipose tissue being identified as the key effector of facultative heat production. Brown fat is less thermogenically active in various obese rodents, and major changes in activity are exhibited under physiological conditions such as lactation and fasting consistent with a general role for the tissue in nutritional energetics. My interests moved to white adipose tissue following the cloning of the Ob gene. Our initial contributions in this area included demonstrating nutritional regulation of Ob gene expression and circulating leptin levels, as well as a regulatory role for the sympathetic nervous system operating through β3-adrenoceptors. My interests subsequently evolved to a wider concern with the endocrine/signalling role of adipose tissue. Inflammation is a characteristic of white fat in obesity with the release of inflammation-related adipokines, and we proposed that hypoxia underlies this inflammatory state. O2-deprivation was shown to have substantial effects on gene expression and cellular function in white adipocytes. The hypoxia studies led to the proposition that O2 should be considered as a critical macronutrient.

Single cell approaches to address adipose tissue stromal cell heterogeneity.

A central function of adipose tissue is in the management of systemic energy homeostasis that is achieved through the co-ordinated regulation of energy storage and mobilization, adipokine release, and immune functions. With the dramatic increase in the prevalence of obesity and obesity-related metabolic disease over the past 30 years, there has been extensive interest in targeting adipose tissue for therapeutic benefit. However, in order for this goal to be achieved it is essential to establish a comprehensive atlas of adipose tissue cellular composition and define mechanisms of intercellular communication that mediate pathologic and therapeutic responses. While traditional methods, such as fluorescence-activated cell sorting (FACS) and genetic lineage tracing, have greatly advanced the field, these approaches are inherently limited by the choice of markers and the ability to comprehensively identify and characterize dynamic interactions among stromal cells within the tissue microenvironment. Single cell RNA sequencing (scRNAseq) has emerged as a powerful tool for deconvolving cellular heterogeneity and holds promise for understanding the development and plasticity of adipose tissue under normal and pathological conditions. scRNAseq has recently been used to characterize adipose stem cell (ASC) populations and has provided new insights into subpopulations of macrophages that arise during anabolic and catabolic remodeling in white adipose tissue. The current review summarizes recent findings that use this technology to explore adipose tissue heterogeneity and plasticity.

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients.

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes.

Comparative evaluation of iron profile in premenopausal obese women with women of normal body mass index

Background: Obesity has become a common problem worldwide due to changes in lifestyle and food habits. Obesity has been associated with many chronic diseases like diabetes mellitus, hypertension, gallstones etc. Excessive adipose tissue through release of adipokines maybe a risk factor for derangements in iron parameters. Authors aim is to study Serum Iron, TIBC, and Serum Ferritin levels in Obese women (BMI >25 kg/m2) in age group of 16 to 45 years and its comparison with normal BMI women.Methods: The case control study was conducted on 100 patients divided into two groups. Group A included 50 patients of obese women (BMI >25 kg/m2) in age group of 16 to 45 years. Group B consists of 50 control patients in similar age group with BMI of 18-23 kg/m2. Serum Iron, TIBC, and Serum Ferritin levels were measured in both groups and compared.Results: The study showed significant derangements of iron parameters in obese women.Serum Ferritin was significantly raised (p<0.001) in obese women whereas Serum Iron and TIBC were significantly decreased in obese women as compared to control group. No significant difference was seen in Serum Hemoglobin and MCV.Conclusions: Obesity is associated with derangements in iron parameters in women of reproductive age group similar to derangements seen in chronic inflammatory state.

THE EFFECTS OF HIRUDOTHERAPY AS A COMPLEMENTARY IN THE TREATMENT OF A PATIENT WITH POLYCYSTIC OVARY SYNDROME: A RARE CASE REPORT

Introduction: The most common endocrine disorder among women in reproductive age is called polycystic ovary syndrome (PCOS). PCOS occurs with elevated levels of androgen and insulin, and excessive release of adipokines from adipose tissue. Aim: The purpose of this case report is to show the positive effect of hirudotherapy application, which is one of the first cases in the literature, in the treatment of PCOS and acne which is very common in women of reproductive age. Method: A 28-year-old female patient who applied to a GETAT Practice Center stated that she was being treated for infertility in her anamnesis. The patient applied for hirudotherapy as a complement to infertility treatment. The patient first read and signed the informed volunteer consent form. After the examinations and examinations, it was decided to apply hirudotherapy to the patient. For hirudotherapy, a total of four small-sized leeches (weight around 0.5 g) were applied to the right and left inguinal areas of the patient and one on the left side of the face. After the application, the examinations and analyses performed on the patient were renewed. Results: After the single session of hirudotherapy in the presented case, blood LH / FSH ratio and prolactin level decreased. Improvement in ovarian cysts was demonstrated radiologically by ultrasound. After hirudotherapy, there was a marked decrease in acne formation on physical examination. Conclusion: The results of this patient, presented as one of the first cases showing the positive effects of hirudotherapy as a complement to treatment in PCOS patients, have a high value in the literature. Larger case series and controlled studies are needed to demonstrate the possible positive effects of hirudotherapy applications on PCOS. Keywords: Hirudotherapy, leech, infertility, biochemistry.

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60 days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.

Amelioration of diet-induced metabolic syndrome and fatty liver with sitagliptin via regulation of adipose tissue inflammation and hepatic Adiponectin/AMPK levels in mice

Chronic consumption of unhealthy diet and sedentary lifestyle induces fatty liver and metabolic complications. Adipocytes get overloaded with lipid succeeding low-grade inflammation and disrupting adipokine release. This research aims to investigate the effect of sitagliptin on white adipose tissue inflammation, adipokine level, metabolic syndrome, and fatty liver through 5’ adenosine monophosphate-activated protein kinase (AMPK) pathway. In sixteen weeks of the experimental protocol, Swiss albino mice were kept in a standard environment and were fed 60% high-fat diet and 20% fructose water (HFFW) where they developed metabolic syndrome features, adipose tissue inflammation, and altered adipokine profile. Sitagliptin was administered for the last eight weeks. They were allocated to following six groups, control diet with regular water (1), HFFW only (2), HFFW and metformin 100 mg/kg (3), HFFW and sitagliptin 10 mg/kg (4), HFFW and sitagliptin 20 mg/kg (5), and HFFW and sitagliptin 30 mg/kg (6). Fasting serum insulin (FSI), glucagon-like peptide-1 (GLP-1), adipokines (adiponectin and leptin), serum lipid profile, hepatic lipid content, and white adipose tissue inflammation were assessed. Protein expression of P-AMPK, P-Acetyl co-a carboxylase (ACC), and mRNA expression of fatty acid metabolism genes were also evaluated in the liver. Sitagliptin significantly and effectively reversed metabolic syndrome complexity. FSI and GLP-1 levels were improved. A significant reduction in hepatic lipid content and oxidative stress was also observed. Also, sitagliptin significantly ameliorated adipose tissue inflammation and adiponectin levels at 20 mg/kg and 30 mg/kg. P-AMPK and P-ACC expression increased significantly. Moreover, expression of fatty acid synthesis genes was down-regulated, and fatty acid oxidation genes were up-regulated. Sitagliptin significantly ameliorated obesity-induced adipose tissue inflammation, metabolic syndrome, and fatty liver via regulation of adiponectin and AMPK levels in obese mice. Also, increased GLP-1 levels would have induced insulin-independent effects on adipose tissue and liver.

New insights into the secretory functions of brown adipose tissue

In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, which is consistent, to some extent, with the earlier recognition of the important secretory role of white fat. The so-called brown adipokines or 'batokines' may play an autocrine role, which may either be positive or negative, in the thermogenic function of brown adipocytes. Additionally, there is a growing recognition of the signalling molecules released by brown adipocytes that target sympathetic nerve endings (such as neuregulin-4 and S100b protein), vascular cells (e.g., bone morphogenetic protein-8b), and immune cells (e.g., C-X-C motif chemokine ligand-14) to promote the tissue remodelling associated with the adaptive BAT recruitment in response to thermogenic stimuli. Moreover, existing indications of an endocrine role of BAT are being confirmed through the release of brown adipokines acting on other distant tissues and organs; a recent example is the recognition that BAT-secreted fibroblast growth factor-21 and myostatin target the heart and skeletal muscle, respectively. The application of proteomics technologies is aiding the identification of new members of the brown adipocyte secretome, such as the extracellular matrix or complement system components. In summary, BAT can no longer be considered a mere producer of heat in response to environment or dietary challenges; it is also an active secretory tissue releasing brown adipokines with a relevant local and systemic action. The identification of the major brown adipokines and their roles is highly important for the discovery of novel candidates useful in formulating intervention strategies for metabolic diseases.

Role of Complement and Complement-Related Adipokines in Regulation of Energy Metabolism and Fat Storage.

Adipose tissue releases many cytokines and inflammatory factors described as adipokines. In obesity, adipokines released from expanding adipose tissue are implicated in disease progression and metabolic dysfunction. However, mechanisms controlling the progression of adiposity and metabolic complications are not fully understood. It has been suggested that expanding fat mass and sustained release of inflammatory adipokines in adipose tissue lead to hypoxia, oxidative stress, apoptosis, and cellular damage. These changes trigger an immune response involving infiltration of adipose tissue with immune cells, complement activation and generation of factors involved in opsonization and clearance of damaged cells. Abundant evidence now indicates that adipose tissue is an active secretory source of complement and complement-related adipokines that, in addition to their inflammatory role, contribute to the regulation of metabolic function. This article highlights advances in knowledge regarding the role of these adipokines in energy regulation of adipose tissue through modulating lipogenic and lipolytic pathways. Several adipokines will be discussed including adipsin, Factor H, properdin, C3a, Acylation-Stimulating Protein, C1q/TNF-related proteins, and response gene to complement-32 (RGC-32). Interactions between these factors will be described considering their immune-metabolic roles in the adipose tissue microenvironment and their potential contribution to progression of adiposity and metabolic dysfunction. The differential expression and the role of complement factors in gender-related fat partitioning will also be addressed. Identifying lipogenic adipokines and their specific autocrine/paracrine roles may provide means for adipose-tissue-targeted therapeutic interventions that may disrupt the vicious circle of adiposity and disease progression. © 2019 American Physiological Society. Compr Physiol 9:1411-1429, 2019.