Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women

Objective: To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin‐stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. Research Methods and Procedures: We studied 33 sedentary, obese (BMI = 32 ± 1 kg/m²) postmenopausal women who completed a 6‐month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3‐hour hyperinsulinemic‐euglycemic clamp (40 mU/m² per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Results: Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid‐thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r² = 0.30) and M/I (r² = 0.33). Discussion: Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Use of Portion‐Controlled Entrees Enhances Weight Loss in Women

Objective: To determine the efficacy of a weight‐loss diet using packaged portion‐controlled entrees compared with a self‐selected diet based on the U.S. Department of Agriculture Food Guide Pyramid (FGP) (United States Department of Agriculture, Center for Nutrition Policy and Promotion, Washington, DC; 1996). Research Methods and Procedures: Sixty healthy women (BMI 26 to 40 kg/m²; 24 to 60 years old) were randomized into two intervention groups for an 8‐week parallel arm study. The portion‐controlled group consumed two frozen entrees daily, plus additional food servings from the FGP. The self‐selected diet group consumed a recommended number of servings from the FGP. Diets were designed to be the same in composition (55% carbohydrate, 25% protein, 20% fat) and energy level (1365 kcal). Each group met weekly to monitor compliance and take measures. Outcomes included weight, body composition by DXA, hip and waist circumference, blood pressure, fasting blood lipids, glucose, insulin, and C‐reactive protein. Significant differences were assessed using repeated measures ANOVA. Results: The portion‐controlled group (n = 26) experienced greater decreases in weight (5.6 ± 2.2 kg or 6.5% vs. 3.6 ± 2.5 kg or 4.2%), fat mass (3.6 ± 1.8 vs. 2.3 ± 1.4 kg), total cholesterol (24.4 ± 21.5 mg/dL or 12.4% vs. 13.0 ± 13.9 mg/dL or 6.7%), and fasting insulin (?1.8 ± 3.7 vs.+0.3 ± 3.8 μU/mL) than the self‐selected diet group (n = 27) (p < 0.05). Discussion: Consumption of portion‐controlled entrees resulted in greater losses of weight and fat, thereby reducing cardiovascular disease risk. Accurate portion control is an important factor in weight loss success, and use of packaged entrees is an effective method of achieving this.     

Effect of Weight Loss on High‐Molecular Weight Adiponectin in Obese Children

Our aim was to determine the influence of weight reduction on total (T‐) and high‐molecular weight (HMW‐) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual‐energy X‐ray absorptiometry (DXA) and serum levels of T‐ and HMW‐adiponectin, resistin, leptin, leptin soluble receptor (sOB‐R), tumoral necrosis factor‐α and interleukin‐6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T‐adiponectin was higher (P < 0.01; confidence interval (+0.04) — (+0.15)) and HMW‐adiponectin lower (P < 0.001; confidence interval (?0.45) ? (?0.21)) in OB children than in controls. A reduction in body fat increased T‐ and HMW‐adiponectin and sOB‐R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin‐6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor‐α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T‐adiponectin (P < 0.05). HMW‐adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T‐adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T‐ nor HMW‐adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T‐ and HMW‐adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.     

In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.     

Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability

Objective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability. Research Methods and Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic‐euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by ¹H‐magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36). Results: Plasma adiponectin was directly associated with insulin sensitivity and high‐density lipoprotein‐cholesterol and inversely with plasma triglycerides but not IMCL. These findings are consistent with adiponectin promoting lipid uptake and subsequent oxidation in muscle and inhibiting TG synthesis in the liver. In multiple regression models that also included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or in combination, adiponectin independently predicted insulin sensitivity, consistent with some of its insulin‐sensitizing effects being mediated through mechanisms other than modulation of lipid metabolism. Because VAT directly correlated with total fat and all three indices of local lipid availability, free fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R² = 0.69, p < 0.0001) contained only VAT (part R² = 0.12, p < 0.002) and adiponectin (part R² = 0.41, p < 0.0001) as independent variables. Discussion: Given the broad range of total adiposity and body fat distribution in our cohort, we suggest that insulin sensitivity is robustly associated with adiponectin and VAT.     

Adiponectin Oligomers and Ectopic Fat in Liver and Skeletal Muscle in Humans

We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total‐, high‐molecular weight (HMW)‐, middle‐molecular weight (MMW)‐, and low‐molecular weight (LMW) adiponectin were quantified by an enzyme‐linked immunosorbent assay. Their relationships with liver‐ and intramyocellular fat, measured using ¹H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = ?0.35, P = 0.012), but not with total‐, MMW‐, or LMW adiponectin. In addition, subjects with fatty liver (liver fat ≥5.56%, n = 15) had significantly lower HMW‐ (P = 0.04), but not total‐, MMW‐, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = ?0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.     

Effect of the mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome

Objective:

Intervention studies on the Mediterranean Diet (MedDiet) have often led to weight loss, which may have contributed to the purported anti‐inflammatory effects of the MedDiet. To investigate the impact of the MedDiet consumed under controlled feeding conditions before (?WL) and after weight loss (+WL) on markers of inflammation in men with metabolic syndrome (MetS).

Design and Methods:

Subjects (N = 26, male, 24–65 years) with MetS first consumed a North American control diet for 5 weeks followed by a MedDiet for 5 weeks both in isocaloric feeding conditions. After a 20‐week weight loss period in free‐living conditions (10 ± 3% reduction in body weight, P < 0.01), participants consumed the MedDiet again under isocaloric‐controlled feeding condition for 5 weeks.

Results:

MedDiet ? WL significantly reduced plasma C‐reactive protein (CRP) concentrations (?26.1%, P = 0.02) and an arbitrary inflammatory score (?9.9%, P = 0.01) that included CRP, interleukin‐6 (IL‐6), IL‐18, and tumor necrosis factor‐α (TNF‐α) compared with the control diet. The MedDiet + WL significantly reduced plasma IL‐6 (?20.7%) and IL‐18 (?15.6%, both P ≤ 0.02) concentrations compared with the control diet but had no further significant impact on plasma CRP concentration. Participants with a reduction in waist circumference ≥8.5 cm after MedDiet + WL showed significantly greater reductions in inflammation markers than those with a change in waist circumference <8.5 cm.

Conclusions:

Thus, consuming MedDiet even in the absence of weight loss significantly reduces inflammation. However, the degree of waist circumference reduction with weight loss magnifies the impact of the MedDiet on other markers of inflammation associated with MetS in men.

     

Intensive weight loss program improves physical function in older obese adults with knee osteoarthritis

Objective: Physical function and body composition in older obese adults with knee osteoarthritis (OA) were examined after intensive weight loss. Research Methods and Procedures: Older obese adults (n = 87; ≥60 years; BMI ≥ 30.0 kg/m²) with symptomatic knee OA and difficulty with daily activities were recruited for a 6‐month trial. Participants were randomized into either a weight stable (WS) or weight loss (WL) program. Participants in WL (10% weight loss goal) were prescribed a 1000 kcal/d energy deficit diet with exercise 3 d/wk. WS participants attended health information sessions. Body composition and physical function (Western Ontario and McMaster University Osteoarthritis Index, 6‐minute walking distance, and stair climb time) were assessed at baseline and 6 months. Statistical analysis included univariate analysis of covariance on 6‐month measurements using baseline values as covariates. Associations between physical function and body composition were performed. Results: Body weight decreased 8.7 ± 0.8% in WL and 0.0 ± 0.7% in WS. Body fat and fat‐free mass were lower for WL than WS at 6 months (estimated means: fat = 38.1 ± 0.4% vs. 40.9 ± 0.4%, respectively; fat‐free mass = 56.7 ± 0.4 vs. 58.8 ± 0.4 kg, respectively). WL had better function than WS, with lower Western Ontario and McMaster University Osteoarthritis Index scores, greater 6‐minute walk distance, and faster stair climb time (p < 0.05). Changes in function were associated with weight loss in the entire cohort. Discussion: An intensive weight loss intervention incorporating energy deficit diet and exercise training improves physical function in older obese adults with knee OA. Greater improvements in function were observed in those with the most weight loss.     

Aerobic exercise maintains regional bone mineral density during weight loss in postmenopausal women

This studyexamines the effects of weight loss by caloric restriction (WL) andaerobic exercise plus weight loss (AEx+WL) on total and regional bonemineral density (BMD) in older women. Healthy,postmenopausal women [age 63 ± 1 (SE) yr] not onhormone-replacement therapy underwent 6 mo of WL(n = 15) consisting of dietarycounseling one time per week with a caloric deficit (250-350kcal/day) or AEx+WL (n = 15)consisting of treadmill exercise three times per week in addition tothe weight loss. Maximal aerobic capacity increased only in the AEx+WLgroup (P < 0.001). Body weight,percent fat, and fat mass decreased similarly in both groups(P < 0.005), with no changesin fat-free mass. Total body BMD (by dual-energy X-rayabsorptiometry) decreased in both groups(P < 0.05). Femoral neck, Ward'striangle, and greater trochanter BMD decreased in the WL group(P  0.05) but were not significantlydifferent after AEx+WL.L₂-L₄BMD did not significantly change in either group. Thus WL andAEx+WL both result in losses of totalbody BMD; however, AEx+WL appears to prevent the loss in regional BMDseen with WL alone in healthy, older women. This suggests that theaddition of exercise to weight-loss programs may reduce the risk forbone loss.

     

Effects of Calcium and Dairy on Body Composition and Weight Loss in African‐American Adults

Objective: Our objective was to determine the effects of dairy consumption on adiposity and body composition in obese African Americans. Research Methods and Procedures: We performed two randomized trials in obese African‐American adults. In the first (weight maintenance), 34 subjects were maintained on a low calcium (500 mg/d)/low dairy (<1 serving/d) or high dairy (1200 mg Ca/d diet including 3 servings of dairy) diet with no change in energy or macronutrient intake for 24 weeks. In the second trial (weight loss), 29 subjects were similarly randomized to the low or high dairy diets and placed on a caloric restriction regimen (?500 kcal/d). Results: In the first trial, body weight remained stable for both groups throughout the maintenance study. The high dairy diet resulted in decreases in total body fat (2.16 kg, p < 0.01), trunk fat (1.03 kg, p < 0.01), insulin (18.7 pM, p < 0.04), and blood pressure (6.8 mm Hg systolic, p < 0.01; 4.25 mm Hg diastolic, p < 0.01) and an increase in lean mass (1.08 kg, p < 0.04), whereas there were no significant changes in the low dairy group. In the second trial, although both diets produced significant weight and fat loss, weight and fat loss on the high dairy diet were ～2‐fold higher (p < 0.01), and loss of lean body mass was markedly reduced (p < 0.001) compared with the low dairy diet. Discussion: Substitution of calcium‐rich foods in isocaloric diets reduced adiposity and improved metabolic profiles in obese African Americans without energy restriction or weight loss and augmented weight and fat loss secondary to energy restriction.     

Energy‐Restricted High‐Fat Diets Only Partially Improve Markers of Systemic and Adipose Tissue Inflammation

This study aimed at investigating whether the weight loss due to energy‐restricted high‐fat diets is accompanied with parallel improvements in metabolic markers and adipose tissue inflammation. Eight‐week‐old C57BL/6J mice were given free access to a low‐fat (LF) or a high‐fat (45% of energy from fat—HF) diet for 6 months. Restricting intake of the HF diet by 30% (HFR) during the last 2 months of the HF feeding trial decreased fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA_IR), and plasma triglyceride levels and improved hepatic steatosis compared to ad libitum HF feeding, indicating an improved metabolic profile. Further, analysis of gonadal white adipose tissue (GWAT) gene expression by microarray and quantitative PCR analyses demonstrated that HFR downregulated expression of genes linked to cell and focal adhesion, cytokine‐cytokine receptor interaction, and endoplasmic reticulum (ER)–associated degradation pathway. However, HFR had no effect on circulating plasminogen activator inhibitor‐1 (PAI‐1) and nonesterified fatty acid levels, which were persistently higher in both HF and HFR groups compared to the LF group. Furthermore, HFR had a negative effect on plasma total adiponectin level. Finally, while HFR decreased GWAT monocyte chemotactic protein‐1 (MCP‐1), interleukin‐2 (IL‐2), and PAI‐1 levels, it did not affect several other cytokines including granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, IL‐1β, IL‐6, and IL‐10. In summary, energy‐restricted high‐fat diets improve insulin sensitivity, while only partially improving markers of systemic and adipose tissue inflammation. In conclusion, our study supports the recommended low‐fat intake for overall cardiovascular health.     

Reversal of Small,Dense LDL Subclass Phenotype by Weight Loss Is Associated With Impaired Fat Oxidation

Adiposity is more prevalent among individuals with a predominance of small, dense low‐density lipoprotein (LDL) (pattern B) particles than among those with larger LDL (pattern A). We tested for differences in resting energy expenditure (REE) and respiratory quotient (RQ) in overweight men with pattern A (n = 36) or pattern B (n = 60). Men consumed a standardized isoenergetic diet for 3 weeks after which a ～9 kg weight loss was induced by caloric deficit for 9 weeks, followed by 4 weeks of weight stabilization. REE and RQ were measured by indirect calorimetry before and after weight loss. Results were analyzed separately in pattern B men who converted to pattern A (B→A; n = 35) and those who did not (B→B; n = 25). At baseline, B→B men had higher trunk fat, triacylglycerol (TG) and insulin concentrations, homeostasis model assessment of insulin resistance (HOMA_IR), and smaller LDL particles compared to B→A men and baseline pattern A men who remained pattern A (A→A; n = 35). REE normalized to fat‐free mass did not change after weight loss. RQ decreased in A→A men, increased in B→A men, and did not change significantly in B→B men after weight loss. Calculated fat oxidation rates paralleled the RQ results. Baseline plasma TG concentrations were positively correlated with RQ and inversely correlated with the magnitude of weight loss achieved for a given prescribed energy reduction in the entire study population. Pattern B men who converted to pattern A with weight loss may have an underlying impairment in fat oxidation that predisposes to both dyslipidemia and an impaired ability to achieve weight loss by energy restriction.     

Endurance Training Per Se Increases Metabolic Health in Young,Moderately Overweight Men

Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy‐reduced diet in 48 sedentary, moderately overweight men who completed a 12‐week intervention program of training (T), energy‐reduced diet (D), training and increased diet (T‐iD), or control (C). An energy deficit of 600 kcal/day was induced by endurance training or diet in T and D and a similar training regimen plus an increased dietary intake of 600 kcal/day defined the T‐iD group. Primary end point was insulin sensitivity as evaluated by HOMA‐IR (mainly reflecting hepatic insulin sensitivity) and hyperinsulinemic, isoglycemic clamps (primarily reflecting peripheral insulin sensitivity). Body mass decreased in T and D by 5.9 ± 0.7 and 5.3 ± 0.7 kg, respectively, whereas T‐iD and C remained weight stable. Total and abdominal fat mass were reduced in an additive manner in the T‐iD, D, and T groups by 1.9 ± 0.3/0.2 ± 0.1, 4.4 ± 0.7/0.5 ± 0.1, and 7.7 ± 0.8/0.9 ± 0.1 kg, respectively. HOMA‐IR was improved in T, D, and T‐iD, whereas insulin‐stimulated glucose clearance and suppression of plasma nonesterified fatty acids (NEFAs) were increased only in the two training groups. Thus, loss of fat mass (diet or training induced) improves hepatic insulin sensitivity, whereas peripheral insulin sensitivity in skeletal muscle and adipose tissue is increased by endurance training only. This demonstrates that endurance training per se increases various metabolic health parameters and that endurance training should preferably always be included in any intervention regimen for improving metabolic health in moderately overweight men.     

Rise of plasma ghrelin with weight loss is not sustained during weight maintenance

Objective: Ghrelin is postulated to be an orexigenic signal that promotes weight regain after weight loss (WL). However, it is not known whether this putative effect of ghrelin is sustained after weight stabilization. The objective of this study was to investigate the relationship of plasma ghrelin concentrations to active WL and weight maintenance in obese subjects. Research Methods and Procedures: This study was a randomized clinical trial, with a 12‐month follow‐up period. Obese Mexican‐American women matched for age and BMI were randomized to a 12‐month WL program (n = 25) or no intervention (controls, n = 23). Interventions included diet, exercise, and orlistat. Body weight and fasting ghrelin, leptin, insulin, and glucose concentrations were measured at baseline and 6 and 12 months. Results: The WL group lost 8.5% of body weight after 6 months and maintained the new weight for the next 6 months. Ghrelin concentrations increased significantly at 6 months but returned to baseline at 12 months. Baseline ghrelin concentrations were directly related to the degree of WL achieved after 12 months. Controls experienced no change in BMI or ghrelin levels. There were no associations between plasma ghrelin and leptin or insulin concentrations. Discussion: Consistent with previous results, ghrelin rises in response to WL, perhaps as a counterregulatory mechanism. However, the present results indicate that ghrelin concentrations return to baseline with sustained weight maintenance, suggesting that its effects are unlikely to regulate long‐term energy balance. Baseline ghrelin concentrations are related to the degree of WL that can be achieved by active weight reduction.     

Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes

It has been suggested that changes in adiponectin levels may contribute to improved insulin sensitivity in insulin-resistant individuals both after weight loss and after treatment with thiazolidinedione compounds. If this is correct, then changes in total circulating adiponectin and/or distribution of its multimeric complexes should coincide with improvements in insulin sensitivity after both interventions. To address this issue, fasting adiponectin concentrations and distribution of adiponectin complexes were measured in plasma samples in 24 insulin-resistant, nondiabetic subjects before and after 3-4 mo of treatment with either rosiglitazone or caloric restriction. The degree of insulin resistance in each group of 12 subjects was equal at baseline and improved to a similar extent ( approximately 30%) after each therapy. Whereas total adiponectin levels increased by nearly threefold and the relative amount of several higher molecular weight adiponectin complexes increased significantly in the rosiglitazone treatment group, there were no discernible changes in adiponectin levels or in the distribution between high or low molecular weight complexes in the weight loss group. These data indicate that, although changes in total adiponectin and several specific adiponectin complexes paralleled improvements in insulin resistance in thiazolidinedione-treated subjects, neither circulating adiponectin concentrations nor multimeric complexes changed in association with enhanced insulin sensitivity after moderate weight loss in 12 insulin-resistant, obese individuals.     

The Effects of Macronutrient Intake on Total and High‐molecular Weight Adiponectin: Results From the OMNI‐Heart Trial

Higher levels of the adipocyte‐specific hormone adiponectin have been linked to increased high‐density lipoprotein (HDL) and lower insulin resistance. This study was conducted to determine the influence of macronutrient intake on adiponectin levels. One hundred and sixty‐four pre‐ and stage‐1 hypertensive adults participated in the Optimal Macro‐Nutrient Intake Heart (OMNI‐Heart) trial, a crossover feeding study originally testing the effects of macronutrients on blood pressure. Participants underwent three 6‐week feeding periods: one rich in carbohydrates (CARB), one rich in monounsaturated fat (MUFA), and one rich in protein (PROT), while maintaining body weight. Their median plasma high molecular weight (HMW) and total adiponectin levels were 2.3 and 8.2 µg/ml, respectively, resulting in an average of 27% HMW adiponectin. Both HMW and total adiponectin levels decreased after baseline while the percent HMW adiponectin remained unchanged. Between diets, the MUFA diet maintained a higher level of both HMW and total adiponectin levels than either the CARB (HMW: +6.8%, P = 0.02; total: +4.5%, P = 0.001) or PROT (HMW: +8.4%, P = 0.003; total: +5.6%, P < 0.001) diets. Changes in total adiponectin levels were positively correlated to changes in HDL cholesterol irrespective of diets (Spearman r = 0.22–0.40). No correlation was found between changes in lipids, blood pressure, or insulin resistance by the homeostasis model assessment (HOMAIR). Macronutrient intake has effects on HMW and total adiponectin levels independent of weight loss. A diet rich in MUFA was associated with higher levels of total and HMW adiponectin in comparison to a carbohydrate‐ or protein‐rich diet. Effects seen in adiponectin paralleled those found with HDL cholesterol.     

Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats

Objective: The anti‐diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin‐sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied. Research Methods and Procedures: Adult female Sprague‐Dawley rats were fed a low‐fat (10% fat) diet or, to elevate body weight (BW), a high‐fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low‐fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice. Results: Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment. Discussion: These results demonstrated that TZD‐induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD‐treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.     

Effect of Energy‐Reduced Diets High in Dairy Products and Fiber on Weight Loss in Obese Adults

Objective: Studies suggest that high‐dairy and high‐fiber/low‐glycemic index diets may facilitate weight loss, but data are conflicting. The effects on weight loss and body fat of a high‐dairy diet and a diet high in dairy and fiber and low in glycemic index were compared with a standard diet. Research Methods and Procedures: Ninety obese subjects were recruited into a randomized trial of three diets designed to provide a calorie deficit of 500 calories/d over a 48‐week period. The study compared a moderate (not low)‐calcium diet with a high‐calcium diet. Results: Seventy‐two subjects completed the study. Significant weight and fat loss occurred with all three diets. A diet with 1400 mg of calcium did not result in greater weight (11.8 ± 6.1 kg) or fat (9.0 ± 6.0 kg) loss than a diet with 800 mg of calcium (10.0 ± 6.8 and 7.5 ± 6.6 kg, respectively). A diet with 1400 mg of calcium, increased fiber content, and fewer high‐glycemic index foods did not result in greater weight (10.6 ± 6.8 kg) or fat (8.5 ± 7.8 kg) loss than the standard diet with 800 mg of calcium. Lipid profile, high‐sensitivity C‐reactive protein, leptin, fasting glucose, and insulin improved significantly, but there were no significant differences between the experimental diets and the control diet. Discussion: We found no evidence that diets higher than 800 mg of calcium in dairy products or higher in fiber and lower in glycemic index enhance weight reduction beyond what is seen with calorie restriction alone.