Prolonged Obesity Research Articles

Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

Association between obesity and atopic dermatitis in childhood: A case-control study

Obesity in children is associated with increased asthma and atopy. We sought to determine whether obesity in childhood or adolescence increases the risk of atopic dermatitis. This retrospective, practice-based, case-control study randomly sampled 414 children and adolescents (age, 1-21 years) with atopic dermatitis between January 2000 and December 2007 and 828 randomly sampled healthy control subjects. Information was obtained from an electronic medical record. Observations were made before the a priori hypothesis. Obesity in children is associated with increased atopic dermatitis (conditional logistic regression: odds ratio, 2.00; 95% CI, 1.22-3.26; P= .006). These atopic dermatitis-predisposing effects are found when obesity started by less than 2 years of age (adjusted odds ratio [aOR], 15.10; 95% CI, 1.51-151.21; P= .02) and 2 to 5 years (aOR, 2.58; 95% CI, 1.24-5.41; P= .01) but not greater than 5 years (aOR, 1.32; 95% CI, 0.66-2.64; P= .43) and when obesity was prolonged for 2.5 to 5 years (aOR, 2.64; 95% CI, 1.13-6.18; P= .03) and greater than 5 years (aOR, 3.40; 95% CI, 1.34-8.63; P= 0.01). Obesity is associated with more severe atopic dermatitis (ordinal logistic regression: aOR, 2.37; 95% CI, 1.24-5.37; P= .01). Obese children who eventually have atopic dermatitis require more frequent pediatrician visits for the management of atopic dermatitis (ordinal logistic regression: aOR, 2.22; 95% CI, 1.12-4.50; P= .03). Prolonged obesity in early childhood is a risk factor for atopic dermatitis. Weight loss might be an important approach for the prevention and treatment of atopic dermatitis in children.

P37 DECREASE OF INSULIN SENSITIVITY FOLLOWS THE DISORDERS – FROM OBESITY, THROUGH PRE-DIABETES, TO NEWLY DIAGNOSED DIABETES

Although obesity is one of the major risk factors for diabetes mellitus, the association of the duration of obesity with glucose intolerance or insulin dysregulation has not yet been clarified. Thirteen articles were picked up from the MEDLINE database by using the four key-word phrases, “duration of obesity,” “duration of overweight,” “prolonged obesity,” and “prolonged overweight.” Although the definition of overweight was similar among the children-based studies (> = 20% or 2 SD over ideal weight), the cutoff point for adults ranged from 25.0 to 30.0kg/m2 of body mass index. With regard to the definition of the duration of obesity, the articles were roughly divided into two groups, with some researchers bearing the definition on the number of years from the onset of overweight and some calculating using the person-years method. The prevalence or incidence of non-insulin-dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT) are probably associated with the duration of obesity. The effect of prolonged obesity on insulin dysregulation is still unclear.

Pathophysiology and Treatment of Obesity Hypertension

Excess weight gain accounts for as much as 65-75% of the risk for essential hypertension and also greatly increases the risk for end stage renal disease (ESRD). Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, and causing volume expansion due to activation of the sympathetic nervous system (SNS) and renin-angiotensin aldosterone system (RAAS), and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of SNS activation in obesity are still unclear but may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin (POMC) pathway. With prolonged obesity, there may be a gradual loss of kidney function that worsens with time, exacerbates hypertension, and makes blood pressure more difficult to control. Lifestyle modifications, including weight reduction and increased physical activity, are essential first steps in the management of obesity hypertension and renal disease. Anti-obesity drugs offer potential pharmacotherapy for obesity hypertension, but current drugs are very limited and additional long-term studies are needed to test their safety and efficacy. Clinical trials are also needed to determine the most effective antihypertensive drugs for obese hypertensive patients. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correcting the metabolic abnormalities and protecting the kidneys from further injury.

The alterations in left ventricular structure and function in young healthy obese women

AbstractObjectives: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women.Background: Severe prolonged obesity in older ad...

Is obesity a major cause of chronic kidney disease?

Excess weight gain is a major risk factor for essential hypertension and for end-stage renal disease (ESRD). Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion because of activation of the sympathetic nervous system and renin-angiotensin system and by physical compression of the kidneys, especially when visceral obesity is present. Obesity also causes renal vasodilation and glomerular hyperfiltration that initially serve as compensatory mechanisms to maintain sodium balance in the face of increased tubular reabsorption. In the long-term, however, these changes, along with the increased systemic arterial pressure, create a hemodynamic burden on the kidneys that causes glomerular injury. With prolonged obesity, there is increasing urinary protein excretion and gradual loss of nephron function that worsens with time and exacerbates hypertension. With the worsening of metabolic disturbances and the development of type II diabetes in some obese patients, kidney disease progresses much more rapidly. Weight reduction is an essential first step in the management of obesity, hypertension, and kidney disease. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correction of the metabolic abnormalities and protection of the kidneys from further injury.

Impact of the obesity epidemic on hypertension and renal disease.

Excess weight gain is a major cause of increased blood pressure in most patients with essential hypertension, and also greatly increases the risk for renal disease. Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, causing volume expansion due to activation of the sympathetic nervous system and renin-angiotensin system, and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of sympathetic nervous system activation in obesity may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin pathway. With prolonged obesity, there may be a gradual loss of nephron function that worsens with time and exacerbates hypertension. Weight reduction is an essential first step in the management of obesity hypertension and renal disease. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correction of the metabolic abnormalities and protection of the kidneys from further injury.

Altered glucose homeostasis in proopiomelanocortin-null mouse mutants lacking central and peripheral melanocortin.

Prolonged obesity frequently leads to insulin resistance and, eventually, to diabetes. This relationship reflects the integration of fat stores and carbohydrate metabolism and the coordination of central nervous system functions, e.g. appetite, and peripheral metabolism. Recent work suggests that the melanocortin system is involved in this integration; specifically, central administration of melanocyte-stimulating hormone (MSH) decreases, whereas lack of central MSH signaling increases, peripheral insulin resistance. Here we asked whether MSH acting in the periphery has a complementary role in insulin resistance. We tested this in a mouse model where the proopiomelanocortin (POMC) gene encoding all of the melanocortins has been genetically deleted. The homozygous POMC-null mouse lacks central as well as peripheral MSH signaling; in addition, it lacks adrenal glands and thus is devoid of corticosterone and epinephrine. Here we report that homozygous POMC mutants have normal serum levels of insulin, normal fasting levels of glucose, and normal clearance of glucose in glucose tolerance tests. Thus, insulin production and sensitivity and glucose uptake in peripheral tissues are functioning normally. However, we found a striking inability of the homozygous POMC mutants to recover from insulin-induced hypoglycemia. This defect was in the glucagon-mediated counterregulatory response. Both peripheral administration of an MSH analog and supplementation with corticosterone alleviated the hypoglycemia after insulin challenge, but did not make the obese POMC mutant mice diabetic. We conclude that, similar to the regulation of body weight homeostasis, the regulation of glucose homeostasis requires the integration of both central and peripheral melanocortin signaling systems.

Functional and structural changes in the kidney in the early stages of obesity.

The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.

Duration of obesity and risk of non-insulin-dependent diabetes mellitus

Although obesity is one of the major risk factors for diabetes mellitus, the association of the duration of obesity with glucose intolerance or insulin dysregulation has not yet been clarified. Thirteen articles were picked up from the MEDLINE database by using the four key-word phrases, "duration of obesity," "duration of overweight," "prolonged obesity," and "prolonged overweight." Although the definition of overweight was similar among the children-based studies (> = 20% or 2 SD over ideal weight), the cutoff point for adults ranged from 25.0 to 30.0 kg/m2 of body mass index. With regard to the definition of the duration of obesity, the articles were roughly divided into two groups, with some researchers bearing the definition on the number of years from the onset of overweight and some calculating using the person-years method. The prevalence or incidence of non-insulin-dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT) are probably associated with the duration of obesity. The effect of prolonged obesity on insulin dysregulation is still unclear.

Medical evaluation and treatment of the obese patient with cardiovascular disease

The incidence of coronary artery disease only weakly correlates with the percent of excess body weight; however, obesity in humans is not a homogeneous condition. Classification of obesity based on anatomic distribution of body fat allows for identification of a group of patients at increased risk for cardiovascular disease. Abdominal (upper body) obesity, measured as the waist/hip ratio, is a strong independent risk factor of cardiovascular disease and should be used to assess a subgroup in need of medical weight loss treatment. A focus on dietary fat intake and the magnitude of overeating “caloric intake” are central to the pathogenesis of cardiovascular disease observed in the obese person. Identification of the process of overeating (magnitude of recent weight gain, episodes of weight cycling) is important in the design of successful medical nutrition treatment programs. A nutrition/medical history that includes age of obesity onset and duration of obesity provides additional criteria for assessment of risk of disease. Childhood-onset obesity and prolonged obesity (>15 years) has been associated with increased cardiovascular disease risk. Recently, grades of obesity based on body mass index have provided a valuable marker for treatment. Each reduction in obesity grade (equal to Δ5 body mass index or Δ11.6 kg) is associated with a decrease in risk of medical illness. The new focus of obesity treatment should be to decrease body weight in 10% to 15% increments (equal to 1 grade) with emphasis on reducing the risk of medical illness and treatment intensity (e.g., number of existing medical visits, hospitalization). Rather than focusing on achieving “ideal body weight,” the goal of any treatment should be to achieve and maintain medically significant weight loss using these criteria.

Skin collagen and thickness in simple obesity.

The effects of stretching of the skin on its collagen content and thickness have been studied in a group of subjects with chronic obesity. Despite the increase in skin surface a normal skin thickness, collagen content, and density were maintained. It is concluded that the skin stretching induced by prolonged obesity led to hypertrophy of collagen and that this had maintained both skin thickness and collagen content. It is not known whether this is due to enhanced synthesis or decreased degradation.