Background/Objectives: The unresolved chronic inflammation of white adipose tissue (WAT) in obesity leads to interstitial deposition of fibrogenic proteins as reparative process. The contribution of omental adipose tissue (oWAT) fibrosis to obesity-related complications remains controversial. The aim of our study was to investigate whether oWAT fibrosis may be related to insulin resistance in severely obese population. Subjects/Methods: Forty obese subjects were studied by glucose clamp before undergoing bariatric surgery and thus stratified according to insulin resistance severity (M-value). From the first (Group B: n=13; M=1.9±0.7 mg kg⁻¹ min⁻¹) and the highest (Group A: n=14; M=4.5±1.4 mg kg⁻¹ min⁻¹) M-value tertiles, which were age-, waist- and body mass index-matched, oWAT samples were then obtained. Gene expression of collagen type I, III and VI, interleukin-6, profibrotic mediators (transforming growth factor (TGF)-β1, activin A, connective tissue growth factor), hypoxia inducible factor-1α (HIF-1α) and macrophage (CD68, monocyte chemotactic protein (MCP)-1, CD86, CD206, CD150) markers were analyzed by quantitative reverse transcription PCR. Adipocyte size and total fibrosis were assessed by histomorphometry techniques. Results: Fibrosis at morphological level resulted significantly greater in Group B compared with Group A, although collagens gene expression did not differ. Notably, collagen VI messenger RNA significantly correlated with collagen I, collagen III, HIF-1α, TGF-β1, CD68, MCP-1 and CD86 transcription levels, supporting their relation with fibrosis development. Conclusions: In conclusion, we show for the first time that human oWAT fibrosis in severe obesity is consistent with a higher degree of insulin resistance measured by glucose clamp. Therefore, collagen deposition could represent a maladaptive mechanism contributing to obesity-related metabolic complications.

People with obesity (PwO) often struggle to achieve and maintain weight loss. This can perpetuate and/or be influenced by feelings of low motivation. This analysis from ACTION-IO data identified factors associated with PwO motivation to lose weight. PwO completed an online survey in 11 countries. Exploratory multinomial logistic regression analyses identified independent variables associated with self-report of feeling motivated versus not motivated to lose weight. Data from 10,854 PwO were included (5,369 motivated; 3,312 neutral; 2,173 not motivated). Variables associated with feeling motivated versus not motivated included (odds ratio [95% confidence interval]): acknowledgement of healthcare professional (HCP) responsibility to contribute to weight loss (2.32 [1.86-2.88]), comfort in talking to their HCP about weight (1.46 [1.24-1.72), agreement that it is easy to lose weight (1.73 [1.30-2.31]), and a goal of reducing risks from excess weight (1.45 [1.22-1.73]). Conversely, if PwO considered obesity less important than other diseases they were less likely to report feeling motivated (0.49 [0.41-0.58]). PwO who reported being motivated to lose weight were more likely to exercise ≥5 times a week versus <1 time a week (2.77 [2.09-3.68]) than those who reported they were not motivated. Positive interactions with HCPs, self-efficacy, setting goals and knowledge of the importance of weight management, in addition to regular exercising, may increase PwO motivation for weight loss. Appropriate HCP support may help PwO who are ready to engage in weight management. NCT03584191.

Obesity is a common, serious, and costly disease. More than 1 billion people worldwide are obese—650 million adults, 340 million adolescents, and 39 million children. The WHO estimates that, by 2025, approximately 167 million people—adults and children—will become less healthy because they are overweight or obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes, and certain types of cancer. These are among the leading causes of preventable, premature death. The estimated annual medical cost of obesity in the United States was nearly $173 billion in 2019 dollars. Obesity is considered the result of a complex interaction between genes and the environment. Both genes and the environment change in different populations. In fact, the prevalence changes as the result of eating habits, lifestyle, and expression of genes coding for factors involved in the regulation of body weight, food intake, and satiety. Expression of these genes involves different epigenetic processes, such as DNA methylation, histone modification, or non-coding micro-RNA synthesis, as well as variations in the gene sequence, which results in functional alterations. Evolutionary and non-evolutionary (i.e., genetic drift, migration, and founder’s effect) factors have shaped the genetic predisposition or protection from obesity in modern human populations. Understanding and knowing the pathogenesis of obesity will lead to prevention and treatment strategies not only for obesity, but also for other related diseases.