Metabolism, Obesity, and Diabetes Mellitus

Abstract

Obesity and diabetes remain leading causes of reduced health span and life span throughout the world. Hence, it is not surprising that these areas are at the center of highly active areas of research. The identification of novel mechanisms underlying these metabolic disorders sets the stage for uncovering new potential therapeutic strategies. In this issue of Highlights in Arteriosclerosis, Thrombosis and Vascular Biology, we review recently published papers in the journal that add to our understanding of causes and consequences of obesity and diabetes and how these disorders impact metabolic function. Collectively, these studies in cultured cells to in vivo animal models to human subjects add to the growing body of evidence that both cell-intrinsic and cell-cell communication mechanisms collaborate in metabolic disorders to cause obesity, insulin resistance and diabetes and its complications. Adipocyte Biology: Effects on Vascular and Inflammatory HomeostasisAdipose tissue is a complex and highly active metabolic organ and adipose dysfunction is linked to cardiovascular disease 18 . Adipose tissues are diverse and specific depots have been characterized as "good fat" versus "bad fat." What accounts for these differences? Indeed, beyond adipocytes, multiple classes of immune cells, such as macrophages, T and B lymphocytes, T regulatory cells and NK cells; nerve tissue; stromovascular cells and endothelial cells (ECs), all housed within a biologically active connective tissue matrix, populate this tissue 19 . Recent studies have identified cell-intrinsic and cell-cell communication pathways linked to obesity and diabetes in adipose and other metabolic tissues, such as liver, skeletal muscle, and brain, and how their properties may affect vascular and inflammatory health and homeostasis. For example, cell-intrinsic roles for adipocytes in metabolic dysfunction were illustrated by studies in mice with adipocytespecific deletion of Nox4 (NADPH oxidase 4), using the Adipoq (Adiponectin) cre recombinase strategy for specific deletion of genes of interest in adipocytes. Mice were fed a high fat/high sucrose diet with added cholesterol. Mice devoid of adipocyte Nox4 exhibited

Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus

“…DM develops in obese and non-obese individuals when b-cell dysfunction manifests, resulting in a reduction in insulin secretion and an exacerbation of the abnormal glucose and lipid metabolism. 20,21 Pearson correlation analysis showed that HOMA-IR positively correlated with SBP, DBP, FPG, FINS, FFA, and TG in the T2DM-N group, indicating that HOMA-IR and IR increase with increases in all these parameters in patients with T2DM but no obesity. In addition, multiple linear regression analysis showed that HOMA-IR increased alongside FFA, TG, and SBP after correcting for FPG, FINS, age, BMI, DBP, fasting C-peptide, TCHO, HDLcholesterol, LDL-cholesterol and other factors.…”

“…DM develops in obese and non-obese individuals when β-cell dysfunction manifests, resulting in a reduction in insulin secretion and an exacerbation of the abnormal glucose and lipid metabolism. 20 , 21 …”

Association Between Elevated Thyroid Peroxidase Antibody and Abdominal Fat Distribution in Patients with Type 2 Diabetes Mellitus

“…Immune cells are important factors in the regulation of adipose tissue function, and the dysfunction of adipose tissue caused by the imbalance of immune homeostasis is an important pathological and physiological mechanism of obesity. 5 Therefore, we hypothesized that obesity, T2DM and AITDs might share some common pathways. There is also further work we will do to explore how thyroid autoimmunity affects obesity and visceral obesity.…”

Factors associated with brain white matter damage in type 2 diabetes mellitus: a tract-based spatial statistics study

“…There is evidence that microvascular dysfunction is one of the key underlying mechanisms that is common in T2DM and began before the onset of T2DM (25). Microvessels are involved in the regulation of many brain functions and are mainly driven by a combination of factors such as high blood sugar, obesity, insulin resistance, and hypertension (26,27). A growing body of research has confirmed that diabetes-related microvascular dysfunction is associated with a higher risk of stroke, cognitive dysfunction, and depression.…”