Effect Of Moderate Weight Loss Research Articles

Effect of a Moderate Weight Loss on Serum Fetuin-A and Markers of Inflammation in Individuals With Obesity

ObjectivesElevated fetuin-A (Fet-A) has been shown to be a risk factor for several metabolic diseases and understanding the effects of moderate weight loss on changes in Fet-A and other inflammatory markers could allow for lifestyle intervention strategies. The association of inflammatory markers and Fet-A with incremental body weight loss is unknown. The objective of the study was to evaluate the association of inflammatory markers, including TNF-alpha (TNF-α), adiponectin, and C-reactive protein (CRP), Fet-A, and it’s phosphorylated form, pFet-A, with incremental body weight loss. MethodsSixteen men achieved a targeted weight loss of 8% to 10% of initial body weight. In this study, we analyzed changes in serum TNF-α, adiponectin, and CRP inflammatory cytokines to changes in serum serum-Fet-A and pFet-A. We also examined the relationship of changes in cytokine profile to alterations in anthropometrics and other metabolic indices. All statistical analyses were performed using GraphPad Prism version 8.0. ResultsA moderate body weight loss of 8% to 10%, significantly decreased serum CRP, but did not affect TNF-α or adiponectin concentrations in individuals with obesity. Serum CRP started to decrease with 4% to 6% body weight loss, demonstrating a mean change in serum CRP concentrations of – 0.15 mg/L and – 0.10 mg/L, for 4%-6% and 8%-10% body weight loss, respectively, for each 1 kg of body weight loss. Weight-loss induced change in serum CRP concentrations were not significantly associated with a decrease in serum Fet-A or pFet-A, although a trend was observed for change in serum pFet-A (r = 0.44, P = 0.09). ConclusionsA moderate weight loss improved serum inflammatory marker C-reactive protein but did not affect TNF-α or adiponectin concentrations in individuals with obesity. These changes were not significantly associated with a decrease in serum pFet-A although a trend was observed. Funding SourcesThis work was supported by the American Diabetes Association (ADA 7–04-JF-36); the Alabama Agricultural Experiment Station (ALA080–052).

Alterations of Serum Ser312-Phosphorylated Fetuin-A from Exercise-Induced Moderate Body Weight Loss in Individuals with Obesity.

Phosphorylated fetuin-A (pFet-A) inhibits insulin action and has been shown to be associated with obesity and insulin resistance. The objective of this cohort study was to assess the effect of incremental body weight loss on alterations in serum pFet-A and indexes of insulin sensitivity. A total of 16 men with obesity attained a targeted weight loss of 8% to 10% of their initial body weight by achieving an energy expenditure/deficit of 2,000 to 2,500 kcal/wk. Anthropometric assessments and blood samples were obtained every 4 weeks. Weight loss was calculated and partitioned as 2% to 4%, 4% to 6%, 6% to 8%, and 8% to 10% compared with initial body weight. Targeted body weight loss of 8% to 10% decreased serum pFet-A, pFet-A:Fet-A ratio, fasting insulin, log(homeostasis model assessment of insulin resistance), quantitative insulin sensitivity check index, adipose insulin resistance, and insulin resistance index significantly. Percent changes in serum pFet-A were associated with percent changes in indexes of insulin sensitivity. Unlike insulin sensitivity indexes, which were altered starting with 6% to 8% weight loss, serum pFet-A levels were significantly decreased by 19.6% starting with 2% to 4% weight loss and decreased by 25.6%, 36.8%, and 42.3% with 4% to 6%, 6% to 8%, and 8% to 10% weight loss, respectively. This study reports for the first time that the insulin-sensitizing effects of moderate weight loss are associated with a reduction in serum pFet-A levels.

The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial

Background: Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. Aim: To examine if the ELF score changes with weight loss. Design and Setting: Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007–2008. Method: Adults with a BMI of 27–35 kg/m² and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. Results: Mean (SD) BMI was 31.10 kg/m² (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: –0.25 to 0.52) despite greater weight loss (difference: –2.66 kg, 95% CI: –5.02 to –0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was –0.15 (95% CI: –0.30 to 0.0002). Conclusion: We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.

The effect of moderate weight loss, with or without (1, 3)(1, 6)-\u03b2-glucan addition, on subcutaneous adipose tissue inflammatory gene expression in young subjects with uncomplicated obesity

PurposeObesity is characterized by insulin resistance and low-grade systemic and adipose tissue (AT) inflammation. It remains unclear whether beneficial effects of weight loss are related to AT inflammation. We aimed to assess the effect of weight loss during low-calorie diet on insulin sensitivity, AT expression of genes associated with inflammation in young subjects with obesity. Furthermore, we estimated the effects of immunomodulatory (1, 3)(1, 6)-β-glucan (BG) on the above parameters.MethodsThe study group comprised 52 subjects with obesity. Twelve-week dietary intervention was applied, with randomization to receive or not 500 mg BG daily. Euglycemic hyperinsulinemic clamp, subcutaneous AT biopsy were performed before and after the program. Twenty normal-weight subjects, examined at baseline, served as a control group.ResultsAt baseline, obese subjects had lower insulin sensitivity, lower AT ADIPOQ, JAK1, and JAK2 expression and higher AT expression of LEP, IL6ST, STAT3, MIF, CCL2, MMP9, and IL18. Forty obese subjects completed dietary intervention program, which resulted in 11.3% weight loss and 27% increase in insulin sensitivity (both p < 0.0001). AT IL6R, IL6ST, JAK1, and JAK2 expression increased, whereas MIF, CCL2, MMP9, and IL18 gene expression did not change in response to weight loss. BG addition had no effect on any of the parameters studied.ConclusionsOur data indicate that reduction in AT inflammation is not required for an improvement in insulin action during weight loss in subjects with uncomplicated obesity. BG does not have effects during dietary intervention.

Long-term effects of a lifestyle intervention and oral glucosamine sulphate in primary care on incident knee OA in overweight women.

The present study was designed to evaluate the effect of a lifestyle intervention aimed to reduce body weight and of oral glucosamine sulphate on the incidence of knee osteoarthritis (OA) after 6-7 years in a population of middle-aged, overweight women, without knee OA at baseline. The Prevention of knee Osteoarthritis in Overweight Females study, ISRCTN42823086, was a randomized controlled trial with a 2 × 2 factorial design. Four hundred and seven women aged 50-60 years with a BMI of ⩾27 kg/m 2 and free of knee OA were randomized. Four hundred and seventy-seven knees from 245 participants were available after a mean follow-up time of 6.6 years. Nineteen per cent of all knees showed incident knee OA. Both interventions showed no significant preventive effect on incident knee OA. Despite the fact that per protocol analyses showed greater differences between both groups for the lifestyle intervention, significance was not reached. A significant effect of losing ⩾5 kg or ⩾ 5% of baseline weight in the first 12 months on the incidence of knee OA according to the primary outcome was found (odds ratio = 0.10; 95% CI: 0.02, 0.41). No significant preventive effect on incident knee OA of either the lifestyle intervention or the glucosamine intervention was found. As a proof of concept, the preventive effect of moderate weight loss in 1 year on the incidence of clinical knee OA is demonstrated. This trial provides important insights for future studies on the prevention of knee OA, which are currently lacking. ISRTCN registry, http://www.isrctn.com , ISRCTN42823086.

Prevention of Incident Knee Osteoarthritis by Moderate Weight Loss in Overweight and Obese Females.

This study evaluated the effect of moderate weight loss on the incidence of knee osteoarthritis (OA) in middle-aged overweight and obese women, without clinical and radiologic knee OA at baseline. A total of 353 women (87%) with followup data available were selected from the Prevention of Knee Osteoarthritis in Overweight Females study, which evaluated the preventive effect of a diet and exercise intervention and of oral glucosamine sulfate on the incidence of knee OA. This was an exploratory proof-of-concept analysis, which compared the incidence of knee OA between women who reached the clinically relevant weight loss target of 5 kg or 5% of body weight after 30 months and those who did not reach this target. The weight loss group showed a significantly lower incidence of knee OA according to the primary outcome measure, which was composed of the American College of Rheumatology criteria (clinical and radiographic), Kellgren/Lawrence grade ≥2, and joint space narrowing ≥1.0 mm (15% versus 20%; odds ratio 0.5, 95% confidence interval 0.3-0.9). Moreover, the weight loss also positively affected several health measures, such as blood glucose level, body fat percentage, and blood pressure. A reduction of ≥5 kg or 5% of body weight over a 30-month period reduces the risk for the onset of radiographic knee OA in middle-aged overweight and obese women. Because of the slow progression of the disease, a longer followup period will be necessary before the number of prevented cases of knee OA by moderate weight loss becomes clinically more relevant.

Effect of moderate weight loss on hepatic, pancreatic and visceral lipids in obese subjects

Objective:To compare the effects of weight loss on visceral and subcutaneous abdominal fat, liver and pancreas lipid content and to test the effects of these changes on metabolic improvement observed after weight loss.Design:Weight-loss program designed to achieve a loss of 7–10% of the initial weight.Subjects:24 obese subjects (13 males and 11 females) with age ranging from 26 to 69 years and body mass index (BMI) 30.2–50.5 kg m−2. Measurements: weight, BMI, waist circumference, body composition as assessed by dual-energy X-ray absorptiometry, metabolic variables, leptin, adiponectin, visceral and subcutaneous abdominal fat, liver and pancreas lipid content as assessed by magnetic resonance were evaluated before and after weight loss achieved by hypocaloric diet.Results:After a mean body weight decrease of 8.9%, BMI, waist circumference, fat mass, all metabolic variables, homeostasis model assessment of insulin resistance (HOMA), alanine amino transferase, gamma glutamyl transpeptidase, high-sensitivity C-reactive protein (hs-CRP) and leptin, but not adiponectin and high-density lipoprotein-cholesterol, significantly decreased (all P<0.01). Visceral and subcutaneos abdominal fat, liver and pancreas lipid content significantly decreased (all P<0.01). Percent changes in liver lipid content were greater (84.1±3%) than those in lipid pancreas content (42.3±29%) and visceral abdominal fat (31.9±15.6%). After weight loss, percentage of subjects with liver steatosis decreased from 75 to 12.5%. Insulin resistance improvement was predicted by changes in liver lipid content independently of changes in visceral fat, pancreas lipid content, systemic inflammation, leptin and gender.Conclusion:Moderate weight loss determines significant decline in visceral abdominal fat, lipid content in liver and pancreas. Reduction of liver lipid content was greater than that of pancreas lipid content and visceral fat loss. Liver lipid content is the strongest predictor of insulin resistance improvement after weight loss.

Weight Loss Reduces Liver Fat and Improves Hepatic and Skeletal Muscle Insulin Sensitivity in Obese Adolescents

Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI >or=95th percentile for age and sex; age 15.3 +/- 0.6 years) before and after moderate diet-induced weight loss (8.2 +/- 2.0% of initial body weight). Weight loss caused a 61.6 +/- 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 +/- 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 +/- 45% increase in insulin-mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet-induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity-related metabolic complications during a standard medical evaluation.

Parameters of Inflammation in Morbid Obesity: Lack of Effect of Moderate Weight Loss

Obesity has been associated with a chronic activation of the acute-phase response. The aims of our study were to investigate whether levels of inflammatory cytokines are higher in obese patients, to evaluate their relationship with metabolic syndrome, and to analyze the effect of moderate weight loss upon their levels. Sixty-seven severe or morbid obese patients were compared with 67 controls. Patients were submitted to a 4-week very low calorie diet followed by a low calorie diet for 2 months. Exclusion criteria were organic disease, ischemic heart disease or stroke, diabetes mellitus, hyperlipidemia, and hypertension. An evaluation was performed before and after the diet, in which fibrinogen, blood count, high-sensitive C-reactive protein (CRP), interleukin 6 (IL-6), and tumoral necrosis factor alpha (TNF-alpha) were measured. The Student t test was employed to compare differences between the groups and Pearson correlation coefficients were calculated. Obese patients showed higher levels of CRP (P < 0.001), IL-6 (P < 0.001), TNF-alpha (P < 0.001), leukocyte (P = 0.001), and neutrophil count (P < 0.001) than controls. In obese patients, inflammatory parameters were significantly correlated with anthropometric parameters and did not differ between obese subjects with or without metabolic syndrome. Moderate weight loss (excess weight loss 19.6%) was achieved through dieting, but no change was observed in any inflammatory parameter. Obesity is associated to a chronic inflammatory state that seems to be due to an increased secretion of cytokines, and this state is not related to the presence of metabolic syndrome. Moderate weight loss does not ameliorate this inflammatory state in the short term.

The effects of obesity and non‐pharmacological weight loss on vascular and ventricular function and structure

The mechanisms by which obesity confers increased cardiovascular risk and the effects of moderate weight loss on cardiovascular health are incompletely understood. We sought to characterize the preclinical changes in cardiac and vascular health that accompany obesity and the influence of lifestyle modification on these parameters. Preclinical markers of vasculopathy in resistance vessels and conduit arteries and left ventricular structure and function were assessed in 39 obese subjects (BMI > 30 kg/m(2)) and 11 healthy weight controls. The influence of serum on cellular adhesion molecule (CAM) expression on human endothelial cells was studied ex vivo in a subgroup of 13 obese and nine healthy weight subjects. These analyses were repeated in all 17 of the obese subjects who complied with 4-9 months of lifestyle modification treatment (six with weight loss >5% and 11 with weight loss <5%). Compared with healthy weight controls, obese subjects had decreased peak hyperaemic forearm blood flow (p = 0.015), increased carotid intima-media thickness (p = 0.009), increased left ventricular wall thickness and volume and evidence of systolic and diastolic dysfunction as assessed using tissue Doppler imaging (S', p = 0.09; E'/A', p = 0.02), and serum from obese subjects increased the intercellular CAM-1 expression on human endothelial cells (p = 0.009). However, arterial endothelial function assessed by flow-mediated dilatation was not altered (p = 0.99). Lifestyle modification treatment resulted in potentially beneficial changes in fibrinogen (p = 0.003), HDL cholesterol (p = 0.05) and soluble vascular CAM-1 (p = 0.06). In subjects with weight loss greater than 5% of body weight, there was also a decrease in low-level inflammation (high-sensitivity C-reactive protein, p = 0.05), lipid peroxidation (thiobarbituric acid-reactive substances, p = 0.05) and triglycerides (p = 0.07). Obesity is associated with widespread alterations in cardiac and vascular structure and function. Moderate short-term weight loss by lifestyle modification results in some beneficial changes in serum profile; however, these are not accompanied by significant alterations to either cardiac or vascular structure and function.

Moderate weight loss in obese women with urinary incontinence: a prospective longitudinal study

This study assessed the effect of moderate weight loss in obese women with urodynamically proven urinary incontinence using the International Consultation on Incontinence recommended outcome measures. Sixty-four incontinent women were offered a weight reduction programme with a target loss of 5-10%. This included a low-calorie diet and exercise. An anti-obesity drug (Orlistat) was offered to those who failed to achieve their target. Forty-two (65%) achieved the target weight loss and had significant reduction in body mass index and girth. Weight loss was associated with significant reduction in pad test loss (median difference, 19 g; 95% confidence interval, 13-28 g; p < 0.001). There was also a clinical and statistically significant improvement in quality of life measures. These results suggest that weight reduction of 5% of initial body weight can improve urinary incontinence severity and its effects on quality of life in obese women.

Cholesterol metabolism and body composition in women: the effects of moderate weight loss

To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and <30% fat. Participants lost an average of 11.7+/-2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86+/-9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31+/-19.4%, P=0.32 and -0.01+/-6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (beta=-5.04, r=0.38; P=0.03, and beta=-147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (beta=6.82, r=0.36; P=0.04 and beta=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption. Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

Interrelations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance: effect of moderate weight loss in older women

Interrelations between fat distribution, muscle lipid infiltration, adipocytokines, insulin resistance, and moderate weight loss have not been investigated in obese older subjects. The objective was to evaluate relations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance in older women and the effects of moderate weight loss. In 35 healthy women aged 58-83 y, body mass index, waist circumference, sagittal abdominal diameter (SAD), and body composition measured by dual-energy X-ray absorptiometry were evaluated. A midthigh single computed tomography scan was performed to determine subcutaneous adipose tissue (AT), intermuscular AT (IAT), muscular tissue, and muscle lipid infiltration, evaluated as low-density lean tissue. Metabolic variables, insulin resistance measured by homeostasis model assessment, adiponectin, leptin, and high-sensitivity C-reactive protein were measured in all subjects and after weight loss in a subgroup of 15 obese women. Waist circumference and SAD were positively correlated with leptin and insulin resistance and negatively correlated with adiponectin. Adiponectin was associated negatively with insulin resistance and positively with HDL cholesterol, whereas leptin was positively associated with insulin resistance and triacylglycerols. Midthigh subcutaneous AT was associated with insulin resistance and leptin, whereas IAT was associated with triacylglycerols. Stepwise regression with insulin resistance as the dependent variable and body mass index, SAD, triacylglycerols, HDL cholesterol, adiponectin, leptin, high-sensitivity C-reactive protein, and midthigh subcutaneous AT as independent variables showed that SAD entered the regression first (R(2) = 0.492) followed by adiponectin (R(2) = 0.63). After moderate weight loss, midthigh subcutaneous AT, IAT, low-density lean tissue, leptin, and insulin resistance decreased significantly; no significant changes in adiponectin were observed. Fat distribution indexes and adiponectin are independently associated with insulin resistance. Even in older women, moderate weight loss improves body fat distribution, muscle lipid infiltration, and insulin resistance. Moderate weight loss results in a significant decrease in leptin but no changes in adiponectin.

Effects of Moderate Weight Loss and Orlistat on Insulin Resistance, Regional Adiposity, and Fatty Acids in Type 2 Diabetes

Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O). Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis. Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se. At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.

Effects of moderate weight loss on anginal symptoms and indices of coagulation and fibrinolysis in overweight patients with angina pectoris.

To evaluate the effects of moderate weight loss, in overweight patients with angina, on plasma coagulation, fibrinolytic indicies and pain frequency. Single-stranded 12-week dietary intervention, an individualised eating plan with quantitative advice delivered by a dietitian. Target weight loss of 0.5 kg per week. Outpatient research clinic. Fifty-four volunteers with angina pectoris were recruited. Five subjects withdrew, so 27 males, 22 females, mean body mass index (BMI) 29.3 (s.d. 4.3) kg/m(2) and age 60.3 (s.d. 6.5) y completed the intervention. Body weight and frequency of anginal pain. Plasma fibrinogen, red cell aggregation (RCA), viscosity, factor VII activity, plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator antigen (t-PA), plasma cholesterol, triglyceride and insulin. After the 12-week dietary intervention period, mean body weight fell by 3.5 (s.d. 2.6) kg or 4.3% (P=0.0001), range -11.7 to +1.7 kg. Mean angina frequency fell by 1.8 (s.d. 3.6) from 3.2 to 1.4 episodes/week (P=0.009) and plasma cholesterol by 0.4 (s.d. 0.7) from 6.3 to 5.9 mmol/l (P=0.0001). HDL cholesterol and triglyceride were unchanged. Of the coagulation and fibrinolytic factors, factor VII activity and RCA were significantly reduced by 5 (s.d. 20), IU/dl (P=0.04) and 1.3 (s.d. 1.3) arbitrary units (P=0.014), respectively. A conventional dietetic intervention, resulting in 4% weight loss, offers the potential to reduce atherosclerotic and thrombotic risk, and to reduce pain frequency, in angina patients. Given the importance of this result in a public health context, these results indicate that this may be a fruitful area for future nutrition research.

Plasma lipids, dehydroepiandosterone sulphate and insulin concentrations in elderly overweight angina patients, and effect of weight loss.

To investigate the effect of moderate weight loss in older overweight subjects with angina pectoris on plasma dehydroepiandosterone sulphate (DHEAS), urinary steroid metabolites, insulin and plasma lipid concentrations. Single stranded study of dietitian led dietary intervention for weight loss in a volunteer outpatient group of 41 subjects with angina (22 males, 19 females), BMI 29.1 s.d. 4.2 kg/m2 aged 61.3 s.d. 6.5 y. Body weight and composition by anthropometry, REE by indirect calorimetry, dietary intake by seven day inventory, plasma DHEAS, insulin and lipids. After 12 weeks dietary supervision there were reductions in body weight (3.3 s.d. 2.3 kg, BMI 1.2 s.d., P = 0.00001) and in reported energy intake (-1179 s.d. 1393 kJ daily, P = 0.0001. No significant change was seen in plasma DHEAS or insulin but there were reductions in plasma cholesterol (-0.5 s.d. 0.6 mmol/l, P = 0.0001) HDL cholesterol (-0.1 s.d. 0.1 mmol/l, P = 0.0048) and triglyceride (-0.1 mmol/l s.d. 0.5, P = 0.055). Weight loss of 4% body weight by conventional dietary means over 12 weeks does not alter plasma DHEAS, urinary steroid metabolites or insulin concentrations, but does reduce plasma cholesterol in older moderately overweight subjects with angina.

Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance.

As obesity is a major risk factor for noninsulin-dependent diabetes mellitus, adipose tissue may generate a mediator that influences the activity of insulin on various target tissues. Recent evidence suggests that a cytokine, tumor necrosis factor-alpha (TNF alpha), may serve this role. This study investigates whether the expression of TNF alpha and its receptors is modulated during drug treatment to reduce insulin resistance. The effects of moderate weight loss by dietary restriction were also examined. We show here that a marked induction of TNF alpha mRNA occurs in adipose tissues from a mouse model of obesity-linked diabetes (KKAy) compared to that in nondiabetic mice (C57). Likewise, RNA transcripts encoding TNF R2 receptors (p75) were significantly increased in fat tissues of the obese diabetic animals. In muscle from these diabetic animals, RNA transcripts encoding both TNF R1 (p55) and R2 were significantly elevated, although R2 transcript abundance was less elevated than in fat. We also observed that the overexpression of mRNA for TNF alpha and both of its receptors could be at least partly normalized by treatment of the diabetic animals with the insulin-sensitizing agent pioglitazone. Treating of the obese diabetic animals by food restriction reduced the expression of mRNA for TNF R2 in muscle, but not fat. These results clearly indicate that gene expression for the TNF systems can be regulated by an insulin-sensitizing drug and reduction of body weight. Such findings support a role for this cytokine in the insulin-resistant diabetic state and show its modulation by therapies that reverse the disorder.

Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance

As obesity is a major risk factor for noninsulin-dependent diabetes mellitus, adipose tissue may generate a mediator that influences the activity of insulin on various target tissues. Recent evidence suggests that a cytokine, tumor necrosis factor-alpha (TNF alpha), may serve this role. This study investigates whether the expression of TNF alpha and its receptors is modulated during drug treatment to reduce insulin resistance. The effects of moderate weight loss by dietary restriction were also examined. We show here that a marked induction of TNF alpha mRNA occurs in adipose tissues from a mouse model of obesity-linked diabetes (KKAy) compared to that in nondiabetic mice (C57). Likewise, RNA transcripts encoding TNF R2 receptors (p75) were significantly increased in fat tissues of the obese diabetic animals. In muscle from these diabetic animals, RNA transcripts encoding both TNF R1 (p55) and R2 were significantly elevated, although R2 transcript abundance was less elevated than in fat. We also observed that the overexpression of mRNA for TNF alpha and both of its receptors could be at least partly normalized by treatment of the diabetic animals with the insulin-sensitizing agent pioglitazone. Treating of the obese diabetic animals by food restriction reduced the expression of mRNA for TNF R2 in muscle, but not fat. These results clearly indicate that gene expression for the TNF systems can be regulated by an insulin-sensitizing drug and reduction of body weight. Such findings support a role for this cytokine in the insulin-resistant diabetic state and show its modulation by therapies that reverse the disorder.

The Effect of Moderate Weight Loss on Overnight Melatonin Secretion

Overnight plasma melatonin level was measured in ten healthy women before and after a 4300 kJ (1000 kcal) diet in which they lost an average 3.1 kg. This weight loss did not significantly alter melatonin levels.

Effect of moderate weight loss on ovarian function assessed by salivary progesterone measurements.

The effects of moderate, voluntary weight loss on ovarian function are studied by monitoring the daily levels of salivary progesterone in 8 dieting women (18 cycles) and 9 age-matched controls (19 cycles). Both groups of women were within normal standards of weight for height, though the dieters were significantly heavier than the controls. Dieters lost weight at an average rate of 1.9 ± 0.3 kg/mo during the study. Dieters' cycles during periods of weight loss (weight loss cycles) have significantly lower peak levels of luteal progesterone (controls 655 ± 46 pmol/L, weight loss 461 ± 67 pmol/L; P < 0.005) and lower average levels of luteal progesterone (controls 287 ± 30 pmol/L, weight loss 214 ± 23 pmol/L; P < 0.005) than do controls. All control cycles were classified as ovulatory by virtue of at least one salivary progesterone reading ≥ 300 pmol/L. Only 62% of the weight loss cycles were classified as ovulatory by this criterion. Where longitudinal weight data are available both the magnitude and duration of progesterone elevation correlates significantly with net weight change during the preceding cycle and show no significant correlation with net weight change during the current cycle. Examination of individual profiles confirms that the most profound suppression of luteal activity usually occurs during post-loss rather than weight loss cycles, even if weight is stable or increasing during the post-loss cycle itself. These results, together with field studies of African horticultural populations, suggest that human ovarian function may be adapted to modulate waiting time to conception in response to trends in energetic balance.