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Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19. [ABSTRACT FROM AUTHOR]

The kidneys play an important role in regulating glucose homeostasis through utilization of glucose, gluconeogenesis, and glucose reabsorption via sodium glucose co-transporters (SGLTs) and glucose transporters. The renal threshold for glucose excretion (RT G ) is increased in patients with type 2 diabetes mellitus (T2DM), possibly due to upregulation of SGLT2 and SGLT1 expression. The resulting increase in renal glucose reabsorption is thought to contribute to the maintenance of hyperglycemia in patients with T2DM. Selective SGLT2 inhibitors reduce the RT G , thereby increasing glucosuria, and have demonstrated favorable efficacy and safety in patients with T2DM inadequately controlled with diet and exercise and other glucose-lowering treatments. [ABSTRACT FROM AUTHOR]

Summary: Our understanding of the mechanisms involved in bodyweight regulation has increased enormously over the last 15 years. Unfortunately, the same time period has seen a trebling in the prevalence of childhood and adult obesity, the health consequences of which are enormous. While the cause for this increase undoubtedly lies in changes to our social environment, genetic factors strongly influence the response to these environmental changes. This article reviews current understanding of the systems controlling energy homeostasis, including the role of leptin and insulin as adiposity signals; neuropeptide Y and α-melanocyte-stimulating hormone as central mediators of the effects of these signals; and gut hormones such as ghrelin, which stimulates appetite, cholecystokinin, peptide YY 3–36, obestatin and oxyntomodulin in regulating meal size. It is hoped that our improving knowledge of the pathways regulating homeostasis and the dysregulation that occurs in obesity will lead to new, more effective treatments. The principal challenge, however, lies in changing the way we live so that obesity is not inevitable in a large proportion of the population. [Copyright &y& Elsevier]

• GIP increases adipose tissue blood flow, lipoprotein lipase activity and storage of triacylglycerol in human adipose tissue. • GIP may increase pro-inflammatory adipokines and adipose tissue inflammation. • Excess GIP secretion may contribute to the development of fatty liver and NAFLD. • Treatment with GIP alone has no glucose lowering benefits in type 2 diabetes. • Combined GIP/GLP-1 agonist has greater effect on improving glycaemic and weight reduction over GLP-1 agonist alone. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) are the two incretin hormones secreted by the enteroendocrine system in response to nutrient ingestion. Compared with GLP-1, GIP is less well studied as a hormone or as a potential pharmacological treatment. Beyond its insulinotropic effects in the pancreas, GIP has important biological actions in many other tissues but its role in dietary fat metabolism and lipid storage in adipose tissue has been most studied. It is still unclear if such effects of GIP on adipose tissue/fat metabolism are protective or deleterious in the long term. Antagonising GIP actions through genetic and chemical disruption in mice models prevented diet induced obesity and improved insulin sensitivity. Whilst such effects of GIP antagonism are yet to be evaluated in humans, recent studies using combined GIP and GLP-1 agonists have shown weight reduction and improved glycaemic control in people with type 2 diabetes (T2D). Therapeutic manipulation of GIP physiology is intriguing in that both agonists and antagonists of GIP are being investigated to explore their potential weight-reducing and other metabolic benefits in people with obesity, T2D and non-alcoholic fatty liver disease (NAFLD). This review will discuss the physiological effects of GIP on fat metabolism in human adipose and other non-adipose tissues such as liver, pancreas, skeletal muscle and heart, describe where the actions of GIP may contribute to the pathophysiology of obesity, T2D and NAFLD and finally describe the therapeutic implications of GIP antagonism and agonism in these conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the effects of rosiglitazone (RSG) on left ventricular ejection fraction (LVEF) in subjects with type 2 diabetes (T2DM) and pre-existing chronic heart failure (CHF) (New York Heart Association [NYHA] functional class I to II). Background: Fluid retention is an important consideration in the use of thiazolidinediones in T2DM patients because it could exacerbate symptoms or precipitate decompensation in those with previously stable CHF. Methods: A total of 224 patients with T2DM and NYHA functional class I to II CHF with LVEF ≤45% were randomized to a 52-week treatment with RSG (4 to 8 mg daily, n = 110) or placebo (PLB) (n = 114) in addition to background antidiabetes therapy. Treatment was uptitrated to achieve target fasting plasma glucose <126 mg/dl; CHF medications were adjusted as appropriate. Results: The LVEF was similar in both groups at baseline (RSG 35.3 ± 6.2%, PLB 35.7 ± 7.8%) and after 52 weeks of treatment (mean difference 1.49%, p = 0.1). Glycemic control was significantly better in the RSG group (mean difference in hemoglobin A1c −0.65%, p < 0.0001). There were significantly more adjudicated events in the RSG group of new or worsening edema (RSG n = 28 [25.5%]; PLB n = 10 [8.8%]; p = 0.005) and increased CHF medication (RSG n = 36 [32.7%], PLB n = 20 [17.5%]; p = 0.037), but no significant difference between groups for other adjudicated end points. A similar proportion of patients withdrew from each treatment group because of adverse events. Conclusions: After 52 weeks of treatment, RSG improved glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA functional class I to II CHF. More fluid-related events occurred with RSG, although these generally did not lead to withdrawal from the study. [Copyright &y& Elsevier]