Neuroimmunology and immunometabolism are burgeoning topics of study, but the intersection of these two fields is scarcely considered. This interplay is particularly prevalent within adipose tissue, where immune cells and the sympathetic nervous system (SNS) have an important role in metabolic homeostasis and pathology, namely in obesity. In the present Review, we first outline the established reciprocal adipose-SNS relationship comprising the neuroendocrine loop facilitated primarily by adipose tissue-derived leptin and SNS-derived noradrenaline. Next, we review the extensive crosstalk between adipocytes and resident innate immune cells as well as the changes that occur in these secretory and signalling pathways in obesity. Finally, we discuss the effect of SNS adrenergic signalling in immune cells and conclude with exciting new research demonstrating an immutable role for SNS-resident macrophages in modulating SNS-adipose crosstalk. We posit that the latter point constitutes the existence of a new field - neuroimmunometabolism.

White adipose tissue is one of the largest organs of the body. It plays a key role in whole-body energy status and metabolism; it not only stores excess energy but also secretes various hormones and metabolites to regulate body energy balance. Healthy adipose tissue capable of expanding is needed for metabolic well-being and to prevent accumulation of triglycerides to other organs. Mitochondria govern several important functions in the adipose tissue. We review the derangements of mitochondrial function in white adipose tissue in the obese state. Downregulation of mitochondrial function or biogenesis in the white adipose tissue is a central driver for obesity-associated metabolic diseases. Mitochondrial functions compromised in obesity include oxidative functions and renewal and enlargement of the adipose tissue through recruitment and differentiation of adipocyte progenitor cells. These changes adversely affect whole-body metabolic health. Dysfunction of the white adipose tissue mitochondria in obesity has long-term consequences for the metabolism of adipose tissue and the whole body. Understanding the pathways behind mitochondrial dysfunction may help reveal targets for pharmacological or nutritional interventions that enhance mitochondrial biogenesis or function in adipose tissue.

Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.

Given the increasing worldwide prevalence of obesity and associated metabolic disturbances, novel therapeutic strategies are imperatively required. A plausible manner to increase energy expenditure is the enhancement of thermogenic pathways in white (WAT) and brown adipose tissue (BAT). In the last 15 years, the identification of novel endogenous mechanisms to promote BAT activity or browning of WAT has pointed at gut microbiota as an important modulator of host metabolic homeostasis and energy balance. In this review, we focused on the relationship between gut microbiota composition and adipose tissue thermogenic program (including BAT activity and browning of WAT) in both physiological and stress conditions. Specifically, we reviewed the effects of fasting, caloric restriction, cold stress and metabolic endotoxemia on both browning and gut microbiota shifts. Mechanistically speaking, processes related to bile acid metabolism and the endocannabinoid system seem to play an important role. In summary, the gut microbiota seems to impact WAT and BAT physiology at multiple levels.

Autophagy is a conserved catabolic process that delivers intracellular proteins and organelles to the lysosome for degradation and recycling. Evidences over the past decades have proved that autophagy participates in cell fate decision and also plays a key role in regulating cellular energy and nutrient stores. Lipid droplets (LDs) are the main lipid storage form in living organisms. The process of autophagic degradation of LDs is referred to lipophagy or macrolipophagy. Lipophagy is not only indispensable for the cellular lipid metabolism but also closely associated with several metabolic disorders such as obesity, hepatic steatosis, atherosclerosis, and so on. Here, we summarize recent progress in understanding the molecular mechanisms of lipophagy regulation and the emerging roles of lipophagy in various biological processes and metabolic disorders.

Adipose tissue is classically recognized as the primary site of lipid storage, but in recent years has garnered appreciation for its broad role as an endocrine organ comprising multiple cell types whose collective secretome, termed as adipokines, is highly interdependent on metabolic homeostasis and inflammatory state. Anatomical location (e.g. visceral, subcutaneous, epicardial etc) and cellular composition of adipose tissue (e.g. white, beige, and brown adipocytes, macrophages etc.) also plays a critical role in determining its response to metabolic state, the resulting secretome, and its potential impact on remote tissues. Compared with other tissues, the heart has an extremely high and constant demand for energy generation, of which most is derived from oxidation of fatty acids. Availability of this fatty acid fuel source is dependent on adipose tissue, but evidence is mounting that adipose tissue plays a much broader role in cardiovascular physiology. In this review, we discuss the impact of the brown, subcutaneous, and visceral white, perivascular (PVAT), and epicardial adipose tissue (EAT) secretome on the development and progression of cardiovascular disease (CVD), with a particular focus on cardiac hypertrophy and fibrosis.

Infiltration of adipose tissue macrophages (ATMs) is a typical feature of obesity, and circulating immune cells may indicate immune cell accumulation. However, it remains unclear whether this is true in the early stages of obesity. This study aimed to define the role of blood monocytes in obesity and the relationship between blood monocytes and ATMs in early-stage obesity. Two groups of male C57BL/6 J mice were fed on a 60 % high-fat diet (HFD) or a 10 % fat normal diet (ND), respectively, and monitored at 1, 2, 3, 7, and 12 weeks. Populations of circulating blood monocytes (CD11b + CD115+), ATMs (F4/80+CD11b+), and their subtypes were collected and analyzed using flow cytometry and immunofluorescence. Some cytokines (TNF-a, IL-1β) and chemokines (CCL2, CCL7) were also analyzed by real-time PCR. HFD induced obesity, dramatic fat expansion, and accumulation of ATMs in mice after 12 weeks. However, an acute and transient reduction of circulating monocyte count, elevated expression of CD11c in ly6c^low monocytes, and concurrent infiltration of ATMs into visceral adipose tissues (VAT) were observed as early as 1 week after initiating HFD. Further, HFD-induced changes in VAT, but not blood monocyte count, were partially reversed upon reverting to ND for 6 weeks. An acute but transient reduction of blood monocyte count was observed at the early stages of HFD feeding, which might be related to early infiltration of macrophages into adipose tissues. We believe that blood monocytes could be targeted as a new obesity treatment following additional studies.

The continued global growth in the prevalence of obesity coupled with the limited number of efficacious and safe treatment options elevates the importance of innovative pharmaceutical approaches. Combinatorial strategies that harness the metabolic benefits of multiple hormonal mechanisms have emerged at the preclinical and more recently clinical stages of drug development. A priority has been anti-obesity unimolecular peptides that function as balanced, high potency poly-agonists at two or all the cellular receptors for the endocrine hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon. This report reviews recent progress in this area, with emphasis on what the initial clinical results demonstrate and what remains to be addressed.

The average risk of venous thromboembolism (VTE) in long haul travellers is approximately 2.8 per 1000 travellers, which is increased in the presence of other VTE risk factors. In pregnant long-haul travellers, little is known in terms of the absolute risk of VTE in these women and, therefore, there is limited consensus on appropriate thromboprophylaxis in this setting. This review will provide guidance to allow practitioners to safely minimize the risk of travel related VTE in pregnant women. The suggestions provided are based on limited data, extrapolated risk estimates of VTE in pregnant travellers, and recommendations from published guidelines. We found that the absolute VTE risk per flight appears to be <1% for the average pregnant or postpartum traveller. In pregnant travellers with a prior history of VTE, a potent thrombophilia or strong antepartum risk factors (e.g. combination of obesity and immobility), the risk of VTE with travel appears to be >1%. Postpartum, the risk of VTE with travel may be >1% for women with thrombophilias (particularly in those with a family history), other transient risk factors and in women with a prior VTE. Based on our findings, we recommend simple measures be taken by all pregnant travellers, such as frequent ambulation, hydration and calf exercises. In those at an intermediate risk, we suggest a consideration of 20-30mmHg compression stockings. In the highest risk group, we suggest careful consideration for low molecular weight heparin thromboprophylaxis. If there are specific concerns, we advise consultation with a thrombosis expert at the nearest local centre.

Analysis of pulmonary arterial hypertension patients in Scotland across 20 years supports a recent French study suggesting there is no protective effect from obesity for this disease, in contrast to emerging evidence from the USA and China http://bit.ly/34WCZ7W.

Fatty Acid Synthase (FASN) is responsible for the de novo synthesis of fatty acids, which are involved in the preservation of biological membrane structure, energy storage and assembly of factors involved in signal transduction. FASN plays a critical role in supporting tumor cell growth, thus representing a potential target for anti-cancer therapies. Moreover, this enzyme has been recently associated with increased PD-L1 expression, suggesting a role for fatty acids in the impairment of the immune response in the tumor microenvironment. Orlistat, a tetrahydrolipstatin used for the treatment of obesity, has been reported to reduce FASN activity, while inducing a sensible reduction of the growth potential in different cancer models. We have analyzed the effect of orlistat on different features involved in the tumor cell biology of the T-ALL Jurkat cell line. In particular, we have observed that orlistat inhibits Jurkat cell growth and induces a perturbation of cell cycle along with a decline of FASN activity and protein levels. Moreover, the drug produces a remarkable impairment of PD-L1 expression. These findings suggest that orlistat interferes with different mechanisms involved in the control of tumor cell growth and can potentially contribute to decrease the tumor-associated immune-pathogenesis.

Although a preponderance of research indicates that increased income inequality negatively impacts population health, several international studies found that a greater income inequality was associated with better population health when measured on a fine geographic level of aggregation. This finding is known as a "Swiss paradox". To date, no studies have examined variability in the associations between income inequality and health outcomes by spatial aggregation level in the US. Therefore, this study examined associations between income inequality (Gini index, GI) and population health by geographic level using a large, nationally representative dataset of older adults. We geographically linked respondents' county data from the 2012 Behavioral Risk Factor Surveillance System to 2012 American Community Survey data. Using generalized linear models, we estimated the association between GI decile on the state and county levels and five population health outcomes (diabetes, obesity, smoking, sedentary lifestyle and self-rated health), accounting for confounders and complex sampling. Although state-level GI was not significantly associated with obesity rates (b = - 0.245, 95% CI - 0.497, 0.008), there was a significant, negative association between county-level GI and obesity rates (b = - 0.416, 95% CI - 0.629, - 0.202). State-level GI also associated with an increased diabetes rate (b = 0.304, 95% CI 0.063, 0.546), but the association was not significant for county-level GI and diabetes rate (b = - 0.101, 95% CI - 0.305, 0.104). Associations between both county-level GI and state-level GI and current smoking status were also not significant. These findings show the associations between income inequality and health vary by spatial aggregation level and challenge the preponderance of evidence suggesting that income inequality is consistently associated with worse health. Further research is needed to understand the nuances behind these observed associations to design informed policies and programs designed to reduce socioeconomic health inequities among older adults.

Non-alcoholic fatty liver disease (NAFLD) is a common disease in Western nations and ranges in severity from steatosis to steatohepatitis (NASH). NAFLD is a genetic-environmental-metabolic stress-related disease of unclear pathogenesis. NAFLD is triggered by caloric overconsumption and physical inactivity, which lead to insulin resistance and oxidative stress. A growing body of evidence indicates that mitochondrial dysfunction plays a critical role in the pathogenesis of NAFLD. Mitochondrial dysfunction not only promotes fat accumulation, but also leads to generation of reactive oxygen species (ROS) and lipid peroxidation, resulting in oxidative stress in hepatocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important modulator of antioxidant signaling that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. The pharmacological induction of Nrf2 ameliorates obesity-associated insulin resistance and NAFLD in a mouse model. Sulforaphane and its precursor glucoraphanin are derived from broccoli sprouts and are the most potent natural Nrf2 inducers-they may protect mitochondrial function, thus suppressing the development of NASH. In this review, we briefly describe the role of mitochondrial dysfunction in the pathogenesis of NASH and the effects of glucoraphanin on its development.