Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.     

Effect of time interval between food intake and exercise on substrate oxidation during exercise in obese and lean children

Background & aims

Exercise induces adaptations in fat metabolism favourable to the treatment of obesity. However, time interval between meal and exercise alters substrate bioavailability and oxidation during exercise. The aim of this study was therefore to investigate the effect of time interval between food intake and exercise on substrate oxidation rates in obese and lean children.

Methods

The metabolic responses to exercise of nine obese children (10.3 ± 1.8 years; %body fat: 36.1 ± 6.1) and seven lean children (9.2 ± 1.6 years; %body fat: 22.2 ± 4.1) were compared 1 h (time interval 1, TI1) and 3 h (TI3) after a standardized breakfast.

Results

Despite significantly lower plasma glucose and insulin concentrations and large effect size suggesting a higher plasma FFA availability (lean, 1.43, obese 0.98), fat oxidation was not significantly increased in TI3 compared to TI1 in both lean and obese children. Fat oxidation contributed marginally to energy expenditure during exercise (<20%) in both conditions and groups but was moderately increased during TI3 compared to TI1 in lean children (effect size: 0.54).

Conclusions

The low contribution of fat oxidation to energy expenditure during exercise in obese and lean children fed 3 h before exercise questions the efficacy of moderate intensity exercise to favourably affect fat balance.     

Energy density but not fat content of foods affected energy intake in lean and obese women

BACKGROUND: Studies have shown that energy intake increases when both the fat content and energy density of the entire diet increases. When the fat content and energy density vary independently of one another, however, energy density, but not fat content, influences intake. OBJECTIVE: The present study examined whether energy intake in lean and obese women is affected when either the energy density or the fat content of a portion of the diet is manipulated and palatability is held constant. DESIGN: In a within-subjects design, 17 lean and 17 obese women consumed meals in the laboratory for four, 4-d test periods. In 3 of these test periods the energy density (4.4 and 6.7 kJ/g) or the fat content (16% and 36% of energy) of compulsory entrees representing 50% of each subject's usual energy intake was manipulated. Additional self-selected foods were consumed ad libitum at meals and as snacks. RESULTS: There were no systematic differences in palatability of the manipulated foods across conditions. Obese and lean participants responded similarly to the dietary manipulations. Intake of self-selected foods at meals was reduced significantly by 16% for both lean and obese subjects in the low- compared with the high-energy-density condition. The fat content of the compulsory foods had no significant effect on energy intake. Ratings of hunger did not differ between diets. CONCLUSION: These results indicate that when a portion of the diet was manipulated, the energy density, but not the fat content, of the foods affected total energy intake at meals in both lean and obese women.     

Fiber and exercise in the treatment of obese adolescents

The changes in body weight, body fat, lean body mass, and the efficiency index were studied in a sample of 80 obese males and females undergoing four different treatments, using two treatment components: an increase in dietary fiber, and energy expenditure through exercise. In both sexes there was a significant effect of exercise upon body weight and an improvement in the efficiency index. There was also a significant interaction between fiber and exercise in girls, but not in boys. This suggests that the eventual effect of dietary fiber is heightened by exercise, as corroborated by significant differences in some of the groups.     

Thermic effect of food during graded exercise in normal weight and obese men

The thermic effect of food during incremental cycle ergometer exercise was compared in six normal weight and six obese men (mean +/- SEM 104 +/- 5% and 160 +/- 11% ideal body weight, respectively). Graded exercise tests were performed after a 12-h fast and 60 min after the start of a 910 kcal mixed meal, on separate days. The thermic of food during exercise, which is the fed minus the fasting oxygen consumption (VO2), was significantly greater for the normal than the obese men at submaximal intensities from O (unloaded cycling) to 100 W (p less than 0.05). The mean slope of the regressions of VO2 (ml . min-1) on power output (W), which reflects the rate of increase in energy expended relative to increases in external work performed, did not differ significantly between the fed and fasting conditions for either group, but the mean (+/- SEM) intercept was significantly higher for the normal, but not the obese men, in the fed than the fasting state (599 +/- 53 versus 497 +/- 47 ml O2 . min-1 for the normal men and 819 +/- 126 versus 821 +/- 145 ml O2 . min-1 for the obese men). These results indicate that the thermic effect of food during exercise, which is virtually absent in the obese men, does not increase significantly across submaximal power outputs for the normal men and therefore does not reflect a significant reduction in efficiency.     

The effect of information about fat content on food consumption in overweight/obese and lean people

This study investigated how fat content labels (high-fat vs. low-fat) influence milkshake consumption in obese/overweight people (n = 23) as compared to lean people (n = 21). Participants 'tasted' two isocaloric milkshakes in a staged taste test on two occasions. On one occasion the milkshakes were labeled high-fat, whereas on the other occasion they were labeled low-fat. The label-effect was in the expected direction of less (estimated future) consumption in the high-fat label condition, but was not significant for the current consumption and not different between groups. Unexpectedly, order (label high-fat first vs. label low-fat first) had a large effect on consumption.     

Effect of daytime on resting energy expenditure and thermic effect of food in obese adolescents.

The aim of this study was to investigate the effect of daytime on resting energy expenditure (REE) and thermic effect of food (TEF), REE and TEF were measured in 11 obese boys (mean age +/- SD 11.9 +/- 1.6 years; body mass index 30.1 +/- 4.0 kg/m2) by indirect calorimetry (SensorMedics 2900) on two consecutive days: early in the morning (7:30 a.m.) on one day and at 12 noon on the other day or vice versa. REE was measured for 30 minutes and TEF for 180 minutes after a 600 kcal liquid meal containing 13% protein, 39% fat and 48% carbohydrates. REE measured in the morning was not statistically different from that measured at noon (2191 +/- 358 vs 2223 +/- 319 kcal/24 hours) and morning values were highly correlated with afternoon values (r2 = 0.805). Therefore we conclude that the effect of daytime is negligible for measurements of REE if the patients are in a postabsorptive state and avoid physical activity and stress 10-12 hours prior to measurements. The thermic effect of food calculated in the morning also was not statistically significantly from values found in the afternoon (8.2 +/- 8.8% in the morning and 6.6 +/- 7.5% in the afternoon). However, because of very high within-patient variability the correlation between morning and afternoon values was weaker than for REE (r2 = 0.289).     

Potentiation of the thermic effect of insulin by exercise: differences between lean, obese, and noninsulin-dependent diabetic men

We studied the effects of prior high-intensity cycle exercise (85% VO2 max) on total energy expenditure (EE) and the thermic effect of insulin (TEI) in normal controls and in obese insulin-resistant and noninsulin-dependent diabetic (NIDDM) subjects. Normal controls, but not obese or NIDDM subjects, showed a significant increase (3-7%) in total EE 12-16 h after exercise (p less than 0.05). Prior exercise increased lipid and decreased glucose oxidation in all groups. During low-dose insulin infusion (40 mU X M2 X min), prior exercise potentiated TEI in control and NIDDM subjects (p less than 0.05), whereas obese subjects showed no response. During high-dose insulin infusion (400 mU X M2 X min), TEI was similar in NIDDM and control subjects but was significantly less in the obese group. In this study, we found a positive correlation between TEI and insulin-stimulated rates of glucose disposal (r = 0.91, p less than 0.001). The predicted cost of glucose storage accounted for 42% of TEI.     

Overweight and obese boys reduce food intake in response to a glucose drink but fail to increase intake in response to exercise of short duration

The effect of short duration exercise (EXR) on food intake (FI) and energy balance (EB) is not well understood in either normal weight (NW) or overweight (OW) and obese (OB) 9-14 years old children. Our purpose was to describe the effects of activity and a glucose drink on short term FI, appetite, and EB in NW, OW, and OB boys. Each boy received in random order either a noncaloric Sucralose sweetened control or glucose (1.0 g·kg(-1) body weight) drink 5 min after either exercise (EXR) or sedentary (SED) activity. Boys exercised for 15 min at their ventilation threshold (V(T)) in experiment 1 or at 25% above their V(T) in experiment 2. FI was measured at an ad libitum pizza meal 30 min after drink consumption. FI was lower after the glucose drink (p < 0.001) but not affected by activity, even though EXR increased appetite (p < 0.001). OW/OB boys ate more total food than NW boys (p = 0.020). EB over the duration of the experiments was reduced by EXR in OW/OB boys (p = 0.013) but not in NW boys in either experiment (p > 0.05). We conclude that intake regulation in OW/OB boys in response to a glucose drink is similar to NW boys, but it may be less responsive to activity.     

Voluntary food intake of lean and obese Zucker rats in relation to dietary energy and nitrogen content

Genetically obese (fa/fa) Zucker rats maintain a normal lean body size but deposit excessive amounts of body fat. Preferential use of substrates for lipid synthesis results in inefficient use of dietary nitrogen for protein deposition. Three studies were carried out to determine whether an increased protein requirement caused hyperphagia and whether young Zucker rats preferentially regulated protein or energy intake. Rats were offered isoenergetic diets with nitrogen contents ranging from 4.5 to 53.2 mg/g, or isonitrogenous diets with energy contents of 2.2, 3.3 or 4.2 kcal/g. In both situations obese rats had significantly higher food intakes than lean rats. Within phenotype the rats maintained an almost constant energy intake so that nitrogen intake was proportional to dietary nitrogen concentration. In a third experiment lean and obese rats were given different proportions of their control protein intake by stomach tube. Energy intake was determined by voluntary consumption of a protein-free diet. Within phenotype energy intake was the same for all levels of protein intake. It appears that obese Zucker rats regulate energy intake at an elevated level and that protein intake is determined by dietary nitrogen content. Hyperphagia does not appear to result from a desire to obtain protein.     

Specific preservation of biosynthetic responses to insulin in adipose tissue may contribute to hyperleptinemia in insulin-resistant obese mice

Obesity is characterized by whole-body insulin resistance, yet the expression of many insulin-stimulated genes, including leptin, is elevated in obesity. These observations suggest that insulin resistance may depend on tissue type and gene. To address this hypothesis, we examined the regulation of immediate-early gene expression in liver and adipose tissue after injection of insulin and glucose, in lean insulin-sensitive, and in A(y)/a obese insulin-sensitive and obese insulin-resistant mice. Expression of hepatic jun-B mRNA was robustly increased after insulin injection in lean insulin-sensitive a/a mice and insulin-sensitive A(y)/a mice. In contrast, induction of hepatic jun-B and c-fos gene expression by insulin was markedly attenuated in obese insulin-resistant mice. Surprisingly, induction of adipose jun-B and c-fos gene expression by insulin was markedly enhanced in obese insulin-resistant mice. Furthermore, the expressions of jun-B and leptin were also enhanced in insulin-resistant mice after injection of glucose. Leptin mRNA was positively correlated with blood glucose levels and jun-B mRNA in lean but not insulin-resistant mice. Multiple regression analysis indicated that the correlation between leptin mRNA and jun-B mRNA was significant even after removing the effect of blood glucose, but the correlation between leptin mRNA and glucose was no longer significant after removing the effect of jun-B mRNA. These data suggest that some impairments in biosynthetic responses to insulin are manifest primarily in the liver, leading to hyperinsulinemia and stimulating the expression of some adipose insulin-stimulated genes, including leptin. These studies demonstrate the utility of immediate-early gene expression in the analysis of biosynthetic mechanisms of insulin resistance.     

Qualitative research using photo-elicitation to explore the role of food in family relationships among obese adolescents

Obesity in adolescence is a major public health issue. Family relationships have an important role, whether in the onset of the condition, its maintenance, or the way in which the problem is approached. Food and family relationships are two major elements in therapeutic care. The subject of the present study is the investigation of the place of food within family relationships among obese adolescents, so as to tailor care strategies. Twelve semi-structured interviews were conducted among adolescents presenting obesity and their parents. The investigation was qualitative, and used photo-elicitation. A photograph produced by the subject is used as the basis for narrative, and the verbal material obtained is analysed using Interpretative Phenomenological Analysis. The results can be categorised along two axes. The first describes the place of food in the one-to-one parent-child relationship; the second describes the organisation of the family group. This study evidenced two possible lines of approach in understanding the place of food in these families. There are major interrelations between food and relationships within the family, so that implications for therapy can be drawn: taking account of bonding between parent and child, and therapeutic orientation towards family functioning rather than towards individual eating patterns.     

A high-protein meal does not improve blood pressure or vasoactive biomarker responses to acute exercise in humans

Blood pressure (BP) responses to exercise yield prognostic information beyond resting BP. While habitual higher dietary protein intake is associated with reduced resting BP, few studies have assessed the impact of high-protein meals on acute BP and vasoactive biomarker responses to exercise. To test the hypothesis that consuming a higher-protein, lower fat meal (HP; 30 g protein, 17 g fat, 52 g carbohydrate) would attenuate the BP response to exercise and result in a more robust post-exercise hypotensive response compared to a lower-protein, higher-fat meal (LP; 13 g protein, 25 g fat, 54 g carbohydrate), we recruited 31 pre-hypertensive subjects to complete this randomized, double-blind, cross-over acute feeding study. One hundred sixty-five minutes after consuming the test HP or LP meal, subjects exercised on a cycle ergometer at 70% VO₂ max for 30 minutes. Blood pressure was measured prior to the meal and periodically before, during, and after exercise for a 315-minute period. Blood samples were periodically collected to quantify plasma arginine, arginine metabolites (asymmetric dimethylarginine, symmetric dimethylarginine; ADMA, SDMA), endothelin-1, nitrates, and nitrites in a subset of subjects (n = 15) as shown in Supplemental Table S1. Consuming the HP meal did not influence the BP responses to exercise, including the post-exercise return to baseline BP or systolic BP area under the curve. While the HP meal resulted in greater postprandial plasma arginine concentrations, ADMA, SDMA, endothelin-1, nitrates, and nitrites were unaltered. These results suggest that consuming a higher-protein, lower-fat meal does not influence BP or vasoactive biomarker responses to exercise compared to a lower-protein, higher-fat meal.     

Degree of habitual mastication seems to contribute to interindividual variations in the glycemic response to rice but not to spaghetti

Previous work by our group showed that the degree of particle breakdown of rice during mastication affects in vitro glycemic potency. The objective of this study was to confirm these in vitro findings in an in vivo model. We hypothesized that the degree of habitual mastication will influence individuals' in vivo blood glucose response (glycemic response, or GR) to carbohydrate foods. Eleven participants came in on six nonconsecutive days to the laboratory and evaluated 2 test foods (rice and spaghetti). Their GR was measured for the subsequent 120 minutes. Mastication parameters were determined using surface electrode electromyography. The particle size distribution of individuals' masticated food was also determined. The intraindividual number of chews per mouthful did not significantly differ for rice and spaghetti (29.9 and 33, respectively), although masticated particle size distribution did (P < .001). Significant correlations between the degree of breakdown during mastication and the GR were observed for rice, but none for spaghetti. Individuals' peak GR (at 45 minutes) correlated significantly with the particles size distribution of their masticated rice (P = .002), and also with the total incremental area under the curve for the GR (r = −0.72; P = .012) and the incremental area under the curve for the first 45 (r = −0.74; P = .010) and 60 minutes (r = 0.73; P = .010) postconsumption. The results suggest that individual differences in mastication may be one of the causes for interindividual differences in the GR to rice but not spaghetti.     

Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

Background

The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.

Methods

SAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.

Results

Plasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.

Conclusions

Fetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.