Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

/pdf/obesity-is-associated-with-macrophage-accumulation-in-130af7ivca.pdf

Obesity is associated with macrophage accumulation in adipose tissue

Recent scientific work has established both a theoretical basis and strong empirical evidence for a causal impact of social relationships on health. Prospective studies, which control for baseline health status, consistently show increased risk of death among persons with a low quantity, and sometimes low quality, of social relationships. Experimental and quasi-experimental studies of humans and animals also suggest that social isolation is a major risk factor for mortality from widely varying causes. The mechanisms through which social relationships affect health and the factors that promote or inhibit the development and maintenance of social relationships remain to be explored.

https://science.sciencemag.org/content/sci/241/4865/540.full.pdf

Social relationships and health.

Background The prevalence of obesity has increased substantially over the past 30 years. We performed a quantitative analysis of the nature and extent of the person-to-person spread of obesity as a possible factor contributing to the obesity epidemic. Methods We evaluated a densely interconnected social network of 12,067 people assessed repeatedly from 1971 to 2003 as part of the Framingham Heart Study. The bodymass index was available for all subjects. We used longitudinal statistical models to examine whether weight gain in one person was associated with weight gain in his or her friends, siblings, spouse, and neighbors. Results Discernible clusters of obese persons (body-mass index [the weight in kilograms divided by the square of the height in meters], ≥30) were present in the network at all time points, and the clusters extended to three degrees of separation. These clusters did not appear to be solely attributable to the selective formation of social ties among obese persons. A person’s chances of becoming obese increased by 57% (95% confidence interval [CI], 6 to 123) if he or she had a friend who became obese in a given interval. Among pairs of adult siblings, if one sibling became obese, the chance that the other would become obese increased by 40% (95% CI, 21 to 60). If one spouse became obese, the likelihood that the other spouse would become obese increased by 37% (95% CI, 7 to 73). These effects were not seen among neighbors in the immediate geographic location. Persons of the same sex had relatively greater influence on each other than those of the opposite sex. The spread of smoking cessation did not account for the spread of obesity in the network. Conclusions Network phenomena appear to be relevant to the biologic and behavioral trait of obesity, and obesity appears to spread through social ties. These findings have implications for clinical and public health interventions.

/pdf/the-spread-of-obesity-in-a-large-social-network-over-32-2y3wfpgr5w.pdf

The Spread of Obesity in a Large Social Network over 32 Years

Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Obesity is defined by a body-mass index (weight divided by square of the height) of 30 kg m(-2) or greater, but this does not take into account the morbidity and mortality associated with more modest degrees of overweight, nor the detrimental effect of intra-abdominal fat. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals, but an epidemic that threatens global well being.

Obesity as a medical problem

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory

http://kidneys.zaslavsky.com.ua/article/download/122220/118980

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.

The Framingham offspring study. Design and preliminary data

The evolution of 303 cases of angina in a general population sample of 5,127 persons was ascertained and revealed that the lot of the angina victim is not a happy one. Prognosis as to survival and progression to more serious coronary manifestations was discouraging in men. One in 4 men with angina can expect to have a coronary attack within 5 years. The risk is half this for women. About 30 percent of those over 55 will die within 8 years, and 44 percent of the coronary deaths will be sudden. Mortality was close to that which follows the posthospital phase of myocardial infarction. Surprisingly, survival in men with uncomplicated angina was no better than that for angina which follows an infarction. Angina was more likely to be the presenting complaint of coronary disease in women (65 percent) than in men (37 percent). In men 45 percent of angina arose out of myocardial infarction compared to 15 percent in women. Half of those sustaining initial myocardial infarctions had angina following it, 31 percent experiencing it for the first time. In those with angina who sustained an infarction, the angina disappeared in only 15 percent of men and no women, a rate lower than the 30 percent spontaneous rate of disappearance. Only 23 percent of infarctions were preceded by angina. Almost 1 in 4 myocardial infarctions were silent or went unrecognized. Such infarctions were rare in persons with prior angina.

Natural history of angina pectoris in the Framingham study: Prognosis and survival

Coronary heart disease (CHD) risk factors were studied in 250 monozygotic (MZ) and 264 dizygotic (DZ) male veteran twin pairs, aged 42-56. All coronary heart disease risk factors studied showed significant correlations in both MZ and DZ twins. Substantial genetic variation was detected for height, blood pressure, glucose intolerance, uric acid, plasma triglyceride, and relative weight but little or no significant genetic variability in low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), total plasma cholesterol or hematocrit was demonstrable. These findings suggest that familial aggregation results from genetic influence on blood pressure, glucose intolerance, uric acid, triglyceride and, possibly, obesity, while largely shared environmental factors contribute to familial similarities in HDL, LDL, total cholesterol and hematocrit.

The nhlbi twin study of cardiovascular disease risk factors: methodology and summary of results

This study examined the relationship of employment status and employment-related behaviors to the incidence of coronary heart disease (CHD) in women. Between 1965 and 1967, a psychosocial questionnaire was administered to 350 housewives, 387 working women (women who had been employed outside the home over one-half their adult years), and 580 men participating in the Framingham Heart Study. The respondents were 45 to 64 years of age and were followed for the development of CHD over the ensuing eight years. Regardless of employment status, women reported significantly more symptoms of emotional distress than men. Working women and men were more likely to report Type A behavior, ambitiousness, and marital disagreements than were housewives; working women experienced more job mobility than men, and more daily stress and marital dissatisfaction than housewives or men. Working women did not have significantly higher incidence rates of CHD than housewives (7.8 vs 5.4 per cent, respectively). However, CHD rates were almost twice as great among women holding clerical jobs (10.6 per cent) as compared to housewives. The most significant predictors of CHD among clerical workers were: suppressed hostility, having a nonsupportive boss, and decreased job mobility. CHD rates were higher among working women who had ever married, especially among those who had raised three or more children. Among working women, clerical workers who had children and were married to blue collar workers were a highest risk of developing CHD (21.3 per cent).

Manning Feinleib

Papers

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.

The Framingham offspring study. Design and preliminary data

Natural history of angina pectoris in the Framingham study: Prognosis and survival

The nhlbi twin study of cardiovascular disease risk factors: methodology and summary of results

Women, work and coronary heart disease: prospective findings from the Framingham heart study.