Proresolving protein Annexin A1: The role in type 2 diabetes mellitus and obesity.

BACKGROUND: Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. METHODS: Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls. RESULTS: DM patients showed similar AnxA1 serum levels when compared to controls. However, when the individuals were stratified according to BMI, AnxA1 levels were higher in individuals with obesity than lean or overweight, and in overweight compared to lean individuals. Moreover, AnxA1 was correlated positively with IL-6 levels. AnxA1 levels were also positively correlated with BMI, waist circumference and waist-to-hip ratio. Furthermore, higher levels of cleaved AnxA1 were observed in adipose tissue from individuals with obesity, independently of DM status. CONCLUSIONS: Enhanced levels of AnxA1 in serum of individuals with obesity suggest an attempt to counter-regulate the systemic inflammation process in this disease. However, the higher levels of cleaved AnxA1 in the adipose tissue of individuals with obesity could compromise its anti-inflammatory and proresolving actions, locally. Considering our data, AnxA1 cleavage in the adipose tissue, despite increased serum levels of this protein, and consequently the failure in inflammation resolution, suggests an important pathophysiological mechanism involved in inflammatory status observed in obesity.

A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery.

OBJECTIVES: The rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is involved in obesity. Few studies have been conducted on patients who underwent bariatric surgery. The aim of this study was to evaluate the influence of FTO SNPs on body weight, body composition, and weight regain during a 60-mo follow-up period after bariatric surgery. METHODS: The rs9939609 was genotyped in 146 individuals using a real-time polymerase chain reaction TaqMan assay. Data for lifestyle, comorbidities, body weight, body mass index (BMI), excess weight loss (EWL), and body composition were obtained before and 6, 12, 18, 24, 36, 48, and 60 mo after surgery. Data were analyzed by comparing two groups of patients according to rs9939609 FTO gene polymorphism. Mixed-regression models were constructed to evaluate the dynamics of body weight, BMI, and EWL over time in female patients. RESULTS: No differences were observed between the groups during the first 24 mo after surgery. After 36, 48, and 60 mo, body weight, fat mass, and BMI were higher, whereas fat-free mass and EWL were lower in the FTO-SNP patient group. Weight regain was more frequent and occurred sooner in the FTO-SNP group. CONCLUSIONS: There is a different evolution of weight loss in obese carriers of the FTO gene variant rs9939609 after bariatric surgery. However, this pattern was evident at only 2 y postbariatric surgery, inducing a lower proportion of surgery success and a greater and earlier weight regain.

Low-Grade Inflammation, Obesity, and Diabetes.

Obesity and its comorbidities are closely related to the inflammatory environment created by expanded adipose tissue. Several mechanisms trigger inflammation in adipose tissue, including excess fatty acids, hypoxia, and activation of the inflammasome. Inflammation is characterized by the abundance of immune cells, particularly M1 macrophages and T lymphocytes, which have increased secretion of proinflammatory cytokines that act to perpetuate systemic inflammation and induce insulin resistance. The gut microbiota is also involved in obesity-induced inflammation via LPS-related endotoxemia that induces cytokine secretion and insulin resistance. Innate lymphoid type 2 cells, regulatory T cells, and interleukine (IL)-10 counteract the inflammation and insulin resistance, establishing classical or metabolically healthy obesity.

Differences in adipose tissue inflammation and oxidative status in C57BL/6 and ApoE-/- mice fed high fat diet.

Apolipoprotein E deficient (Apo E-/-) mice are more resistant to the development of obesity compared to C57BL/6 wild type mice. They also hold a high basal oxidative status due to the loss of antioxidant action of apolipoprotein E. Since obesity is also an inducer of inflammation, we studied the effect of high-fat diet on obesity and oxidative stress in C57BL/6 and Apo E-/- mice for 9 weeks. The results confirmed that Apo E-/- mice fed high-fat diet are more resistant to the increase of both body weight and adiposity compared to C57BL/6 mice. Despite this, Apo E-/- mice presented a higher basal oxidative stress that was enhanced by high-fat diet. Macrophage infiltration, macrophage forming crown-like structures and proinflammatory adipokines (interleukin 6 and tumor necrosis factor alpha) were all higher in adipose tissue from Apo E-/- compared to C57BL/6 mice, regardless of diet type. In conclusion, although Apo E-/- mice are more resistant to becoming obese, they develop more severe adipose tissue inflammation companied by its consequences.