Weight Loss During 12 Weeks' Ad Libitum Carbohydrate-Rich Diet in Overweight and Normal-Weight Subjects at a Danish Work Site

The effect of 12 weeks' ad libitum carbohydrate-rich, low-fat diet on total body weight, lean body mass, and fat mass was studied in a group of healthy subjects at a Danish work-site (I) (n=50, BMI = 28.4 ± 0.7 kg/m²). Sixteen subjects served as controls (C) (BMI = 27.0 ± 1.0 kg/m²). After 12 weeks the I subjects had decreased their fat intake from 39.0 ± 1.1 energy-% (E%) to 28.0 ± 1.2 E% and increased their carbohydrate intake from 46.0 ± 1.1 E% to 56.4 ± 1.1 E% (p < 0.05 vs. C). Moreover, a significant loss of body weight (4.2 ± 0.4 kg) and fat mass (4.4 ± 0.6 kg) was observed in I (p < 0.05 vs. C). The weight loss in I was not regained at 24 and 52 weeks' follow-up (82% of I participating) compared to baseline. The cost per kg lost weight amounted to $14.7/person. In conclusion, instructions at a work site in ad libitum intake of a carbohydrate-rich, low-fat diet resulted in a significant loss of body weight and fat mass in overweight and normal-weight subjects.     

Respiratory Quotient Predicts Fat Mass Gain in Premenopausal Women

High respiratory quotient (RQ) has been associated with fat mass (FM) gain in some, but not all studies. Variability among results may reflect differences in the RQ variable measured (fasting vs. 24‐h) or may be due to differences in control for factors that affect RQ, such as diet, energy balance, circulating insulin, and insulin sensitivity. The objective of this study was to determine whether different RQ values (fasting, sleeping, nonsleeping, and 24‐h) would predict change in FM over 2 years in obesity‐prone women, controlling for diet and adjusting for energy balance, circulating insulin, and insulin sensitivity. Participants were 33 previously overweight premenopausal women. Fasting, sleeping, nonsleeping, and 24‐h RQ values were measured during controlled‐diet conditions by respiratory chamber calorimetry. Intravenous glucose tolerance tests were also performed to adjust for fasting insulin, acute insulin response to glucose, and insulin sensitivity. Over the following 2 years, changes in FM were tracked annually by dual energy X‐ray absorptiometry. High nonsleeping RQ (NSRQ) predicted 2‐year change in FM independently of energy balance, circulating insulin, and insulin sensitivity. This observation suggests that low postprandial fat oxidation may uniquely predispose obesity‐prone individuals to accrual of adipose tissue.     

Maternal Insulin Sensitivity During Pregnancy Predicts Infant Weight Gain and Adiposity at 1 Year of Age

Emerging evidence suggests that fetal environmental exposures impact on future development of obesity. The objectives of this study were to assess the relationships between (i) maternal insulin sensitivity and glucose tolerance status in pregnancy and (ii) early infant weight gain and adiposity in the first year of life. In this prospective cohort study, 301 women underwent oral glucose tolerance testing for assessment of glucose tolerance status and insulin sensitivity (IS_OGTT) in pregnancy. Their infants underwent anthropometric assessment at 12 months of age, including determination of weight gain in the first year of life and sum of skinfold thickness (SFT), a measure of infant adiposity. Infant weight gain and sum of SFT at 12 months did not differ according to maternal glucose tolerance status. On univariate analyses, weight gain from 0 to 12 months and sum of SFT were negatively associated with maternal IS_OGTT during pregnancy. On multiple linear regression analysis, negative independent predictors of weight gain from 0 to 12 months were maternal IS_OGTT during pregnancy (t = ?2.73; P = 0.007), infant female gender (t = ?3.16; P = 0.002), and parental education (t = ?1.98; P = 0.05), whereas white ethnicity was a positive independent predictor (t = 2.68; P = 0.008). Maternal IS_OGTT (t = ?2.7; P = 0.008) and parental education (t = ?2.58; P = 0.01) were independent negative predictors of sum of SFT at 12 months. Independent of maternal glucose tolerance status, maternal insulin resistance during pregnancy is associated with increased infant weight gain and adiposity over the first year of life. Further longitudinal study to evaluate obesity in this group of children will increase our understanding of the contribution of the intrauterine environment to their long‐term health.     

Circadian Timing of Food Intake Contributes to Weight Gain

Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high‐fat diet only during the 12‐h light phase gain significantly more weight than mice fed only during the 12‐h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today.     

Effect of High Sugar Intake on Glucose Transporter and Weight Regulating Hormones in Mice and Humans

Objective

Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans.

Methods

Five iso-caloric diets, enriched with liquid (in water 30% vol/vol) or solid (in diet 65% g/g) fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5) and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression.

Results

In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001). Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals.

Conclusions

We show that the form of sugar intake (liquid versus solid) is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals.     

Increasing Fruit and Vegetable Intake and Decreasing Fat and Sugar Intake in Families at Risk for Childhood Obesity

Objective: The goal of this study was to evaluate the effect of a parent‐focused behavioral intervention on parent and child eating changes and on percentage of overweight changes in families that contain at least one obese parent and a non‐obese child. Research Methods and Procedures: Families with obese parents and non‐obese children were randomized to groups in which parents were provided a comprehensive behavioral weight‐control program and were encouraged to increase fruit and vegetable intake or decrease intake of high‐fat/high‐sugar foods. Child materials targeted the same dietary changes as their parents without caloric restriction. Results: Changes over 1 year showed that treatment influenced targeted parent and child fruit and vegetable intake and high‐fat/high‐sugar intake, with the Increase Fruit and Vegetable group also decreasing their consumption of high‐fat/high‐sugar foods. Parents in the increased fruit and vegetable group showed significantly greater decreases in percentage of overweight than parents in the decreased high‐fat/high‐sugar group. Discussion: These results suggest that focusing on increasing intake of healthy foods may be a useful approach for nutritional change in obese parents and their children.     

Dietary Intake of Whole and Refined Grain Breakfast Cereals and Weight Gain in Men

Objective: Prospective studies have suggested that substituting whole grain for refined grain products may lower the risk of overweight and obesity. Breakfast cereal intake is a major source of whole and refined grains and has also been associated with having a lower BMI. The aim of this study was to prospectively assess the association between whole and refined grain breakfast cereal intakes and risk of overweight (BMI ≥ 25 kg/m²) and weight gain. Research Methods and Procedures: We examined 17, 881 U.S. male physicians 40 to 84 years of age in 1982 who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline and reported measures of breakfast cereal intake, weight, and height. Results: Over 8 and 13 years of follow‐up, respectively, men who consumed breakfast cereal, regardless of type, consistently weighed less than those who consumed breakfast cereals less often (p value for trend = 0.01). Whole and refined grain breakfast cereal intake was inversely associated with body weight gain over 8 years, after adjustment for age, smoking, baseline BMI, alcohol intake, physical activity, hypertension, high cholesterol, and use of multivitamins. Compared with men who rarely or never consumed breakfast cereals, those who consumed ≥1 serving/d of breakfast cereals were 22% and 12% less likely to become overweight during follow‐up periods of 8 and 13 years (relative risk, 0.78 and 0.88; 95% confidence interval, 0.67 to 0.91 and 0.76 to 1.00, respectively). Discussion: BMI and weight gain were inversely associated with intake of breakfast cereals, independently of other risk factors.     

Mechanisms Preserving Insulin Action during High Dietary Fat Intake

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The Angiogenic Inhibitor TNP-470 Decreases Caloric Intake and Weight Gain in High-Fat Fed Mice

The angiogenic inhibitor TNP-470 attenuates high-fat diet-induced obesity; however, it is not clear how the compound alters energy balance to prevent weight gain. Five-week-old C57BL/6J mice were fed high-fat diet (45% energy from fat) for 6.5 weeks and treated with TNP-470 (20 mg/kg body weight; n = 7) or vehicle (saline; n = 7). Control mice (n = 8) received standard chow and sham injection. TNP-470 mice initially gained weight, but by day 5 body weight was significantly less than high-fat fed (HFF) mice and not different from that of chow-fed mice, an effect maintained to the end of the study (28.6 ± 0.6 vs. 22.4 ± 0.6 and 22.2 ± 0.5 g). Percent body fat was reduced in TNP-470 compared to HFF mice, but was greater than that of chow mice (34.0 ± 1.5, 23.9 ± 1.5, and 17.0 ± 1.4%, P < 0.05). Food intake in TNP-470-treated mice was less (P < 0.05) than that in HFF mice by day 5 of treatment (2.5 ± 0.1 vs. 2.8 ± 0.1 g/mouse/day) and remained so to the end of the study. Twenty-four hours energy expenditure was greater (P < 0.05) in TNP-470 than HFF or chow mice (7.05 ± 0.07 vs. 6.69 ± 0.08 vs. 6.79 ± 0.09 kcal/kg/h), an effect not explained by a difference in energy expended in locomotion. Despite normalization of body weight, TNP-470 mice exhibited impaired glucose tolerance (area under the curve 30,556 ± 1,918 and 29,290 ± 1,584 vs. 24,421 ± 903 for TNP, HFF, and chow fed, P < 0.05). In summary, the angiogenic inhibitor TNP-470 attenuates weight gain in HFF mice via a reduction in caloric intake and an increase in energy expenditure.     

S 23521 Decreases Food Intake and Body Weight Gain in Diet‐Induced Obese Rats

Objective: To investigate the effect of S 23521, a new glucagon‐like peptide‐1‐(7‐36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis. Research Methods and Procedures: Lean and diet‐induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 μg/kg) or subcutaneously (100 μg/kg) for 14 and 20 days, respectively. Because the low‐dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end‐points. Results: Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle‐treated counterparts (3401 ± 65 vs. 3898 ± 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein‐1, uncoupling protein‐3, leptin, resistin, and peroxisome proliferator‐activated receptor (PPAR)‐γ were observed. Discussion: S 23521 is an effective glucagon‐like peptide‐1‐(7‐36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet‐induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.     

Alcohol Intake and 8‐Year Weight Gain in Women: A Prospective Study

Objective: To examine prospectively the relationship between alcohol and 8‐year weight gain in women. Research Methods and Procedures: A prospective study of 49, 324 women 27 to 44 years old who did not have a history of cardiovascular disease, cancer, or diabetes, who were not pregnant during the study period, and who reported weights in 1991 and 1999. Results: In cross‐sectional analyses, there was a significant inverse relationship between alcohol and BMI even after adjustment for dietary factors and a wide range of confounders. In multivariate prospective analyses, a nonlinear relationship was seen between alcohol and weight gain (≥5 kg) in all women. Compared with nondrinkers, the adjusted relative odds [95% confidence interval (CI)] of weight gain according to grams per day were 0.94 (0.89, 0.99) for those consuming 0.1 to 4.9 g/d, 0.92 (0.85, 0.99) for 5 to 14.9 g/d, 0.86 (0.76, 0.78) for 15 to 29.9 g/d, and 1.07 (0.89, 1.28) for those consuming 30+ g/d (p < 0.0001 for quadratic trend). Women who continued to drink heavily and those who became heavy drinkers showed similar increased odds of weight gain. The increased odds of weight gain associated with heavy drinking (30+ g/d) were most marked in the younger women (<35 years) (odds ratio 1.64; 5% CI 1.03 to 2.61). In African‐American women, light drinking was associated with increased odds of weight gain compared with nondrinkers (odds ratio = 2.43; 95% CI 1.22 to 4.82) Discussion: Our data suggest that light to moderate drinking (up to 30 g/d) is not associated with weight gain in women except possibly in African‐American women. Heavier drinking may promote weight gain in women.     

LY226936 Administered Orally and Centrally to Obese Zucker Rats Suppresses Food Intake and Body Weight Gain

LY226936, methylcarbamothoic acid-S-(4,5-dihydro-2-thiazolyl) ester, is a new compound that, when administered to obese Zucker rats, caused reduced food intake. LY226936 reduced the food consumption after a single oral dose of 50 and 100 mg/kg. On chronic oral administration to meal-fed obese (5 to 35 mg/kg. once daily) and to fed obese and lean (15 mg/kg. twice daily) Zucker rats, LY226936 reduced food intake and body weight gain for periods ranging from 40 to 48 days. The effect on both parameters was statistically significant. There is no evidence in our studies that tolerance to the actions of LY226936 developed. LY226936 decreased the consumption of both high carbohydrate and high fat diets. Food consumption of meal-fed obese Zucker rats was reduced significantly each time a single dose of 10 ugm LY226936 per rat was infused intracerebroventricularly. None of the receptors studied (mu and kappa opioid, CCK, serotonin, neuropeptide Y, galinin, N-methyl-D-aspartic acid) appeared to bind LY226936 and therefore, appear not to be involved in the depression of food intake by the obese Zucker rat.