Failure of dietary fat intake to promote fat oxidation: a factor favoring the development of obesity.

Seven young men spent three nights and 2 d in a respiration chamber where their rates of energy expenditure and substrate oxidation were continuously measured by indirect calorimetry. During the first 24 h they ingested a mixed maintenance diet containing 35% of calories as fat. An additional amount of 106 +/- 6 g fat/24 h (means +/- SD) was added to this diet during the following 36 h. The fat supplement (987 +/- 55 kcal/d) did not alter 24-h energy expenditure (2783 +/- 232 vs 2820 +/- 284 kcal/d) and failed to promote the use of fat as a metabolic fuel (fat oxidation 1032 +/- 205 vs 1042 +/- 205 kcal/d). The overall energy balance was closely correlated with the fat balance (r = 0.96, p less than 0.001) but not with the carbohydrate balance (r = -0.12, NS). These data indicate that substantial imbalances between intake and oxidation are much more likely for fat than for carbohydrate.

The effect of ethanol on fat storage in healthy subjects.

BACKGROUND: Ethanol can account for up to 10 percent of the energy intake of persons who consume moderate amounts of ethanol. Its effect on energy metabolism, however, is not known. METHODS: We studied the effect of ethanol on 24-hour substrate-oxidation rates in eight normal men during two 48-hour sessions in an indirect-calorimetry chamber. In each session, the first 24 hours served as the control period. On the second day of one session, an additional 25 percent of the total energy requirement was added as ethanol (mean [+/- SD], 96 +/- 4 g per day); during the other session, 25 percent of the total energy requirement was replaced by ethanol, which was isocalorically substituted for lipids and carbohydrates. RESULTS: Both the addition of ethanol and the isocaloric substitution of ethanol for other foods reduced 24-hour lipid oxidation. The respective mean (+/- SE) decreases were 49.4 +/- 6.7 and 44.1 +/- 9.3 g per day (i.e., reductions of 36 +/- 3 percent and 31 +/- 7 percent from the oxidation rate during the control day; P less than 0.001 and P less than 0.0025). This effect occurred only during the daytime period (8:30 a.m. to 11:30 p.m.), when ethanol was consumed and metabolized. Neither the addition of ethanol to the diet nor the isocaloric substitution of ethanol for other foods significantly altered the oxidation of carbohydrate or protein. Both regimens including ethanol produced an increase in 24-hour energy expenditure (7 +/- 1 percent with the addition of ethanol, P less than 0.001; 4 +/- 1 percent with the substitution of ethanol for other energy sources, P less than 0.025). CONCLUSIONS: Ethanol, either added to the diet or substituted for other foods, increases 24-hour energy expenditure and decreases lipid oxidation. Habitual consumption of ethanol in excess of energy needs probably favors lipid storage and weight gain.

Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.

IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Metabolic Post-feeding Changes in Fat Body and Hemolymph of Dipetalogaster maximus (Hemiptera:Reduviidae)

Lipids and glycogen in fat body as well as the modifications in the wet weight of this organ were evaluated in an unfed insect, Dipetalogaster maximus, on day 5 after adult ecdysis (time 0) and during a 30-day period after ingestion of blood meal. Total lipids, high density lipophorin (HDLp), carbohydrates, total proteins and uric acid were determined in the hemolymph during the same period. Fat body wet weight was maximum on day 10 post-feeding and represented on day 30 only 42% of the maximum weight. Lipids stored in the fat body increased up to day 15 reaching 24% of the total weight of tissue. Glycogen was maximum on day 20, representing approximately 3% of the fat body weight. HDLp represented at all times between 17-24% of the total proteins, whose levels ranged between 35 and 47 mg/ml. Uric acid showed at 20, 25 and 30 days similar levels and significantly higher than the ones shown at days 10 and 15. Hemolymphatic lipids fluctuated during starvation between 3-4.4 mg/ml and carbohydrates showed a maximum on day 15 after a blood meal, decreasing up to 0.26 mg/ml on day 25. The above results suggest that during physiological events such as starvation, the availability of nutrients is affected, involving principally the fat body reserves

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10-3 to 0.76×10-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

Haemolymph and Fat Body Metallo-protease Associated with Enterobacter cloacae Infection in the Bloodsucking Insect, Rhodnius prolixus

Analysis of zymograms with SDS-polyacrilamide gel electrophoresis containing gelatin as substrate, and performed on samples of haemolymph or fat body taken from Rhodnius prolixus inoculated or not with Enterobacter cloacae, demonstrated distinct patterns of protease activities: (i) in the haemolymph two proteases were induced in insects inoculated with bacteria; (ii) two proteases were detected in the fat bodies derived from non-inoculated controls or insect inoculated with sterile culture medium; (iii) haemolymph and fat body had both the same apparent molecular weights proteases (46 and 56 kDa); and (iv) these enzymes were characterized as metallo-proteases. The association of these enzymes in Rhodnius infected with bacteria was discussed.

Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet.

OBJECTIVE-Obesity and associated pathologies are major global health problems. Transforming growth factor-beta/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic beta-cell function. However, the systemic effects of Smad3 deficiency on adiposity and insulin resistance in vivo remain elusive. This study investigated the effects of Smad3 deficiency on whole-body glucose and lipid homeostasis and its contribution to the development of obesity and type 2 diabetes.RESEARCH DESIGN AND METHODS-We compared various metabolic profiles of Smad3-knockout and wild-type mice. We also determined the mechanism by which Smad3 deficiency affects the expression of genes involved in adipogenesis and metabolism. Mice were then challenged with a high-fat diet to study the impact of Smad3 deficiency on the development of obesity and insulin resistance.RESULTS-Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity. Chromatin immunoprecipitation assay revealed that Smad3 deficiency increased CCAAT/enhancer-binding protein beta-C/EBP homologous protein 10 interaction and exerted a differential regulation on proliferator-activated receptor beta/delta and proliferator-activated receptor gamma expression in adipocytes. Focused gene expression profiling revealed an altered expression of genes involved in adipogenesis, lipid accumulation, and fatty acid beta-oxidation, indicative of altered adipose physiology. Despite reduced physical activity with no modification in food intake, these mutant mice were resistant to obesity and insulin resistance induced by a high-fat diet.CONCLUSIONS-Smad3 is a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes, suggesting that Smad3 may be a potential target for the treatment of obesity and its associated disorders.

Optimal 3-T MRI for depiction of the finger A2 pulley: comparison between T1-weighted, fat-saturated T2-weighted and gadolinium-enhanced fat-saturated T1-weighted sequences

OBJECTIVE: To compare three spin-echo sequences, transverse T1-weighted (T1WI), transverse fat-saturated (FS) T2-weighted (T2WI), and transverse gadolinium-enhanced (Gd) FS T1WI, for the visualisation of normal and abnormal finger A2 pulley with magnetic resonance (MR) imaging at 3 tesla (T). MATERIALS AND METHODS: Sixty-three fingers from 21 patients were consecutively investigated. Two musculoskeletal radiologists retrospectively compared all sequences to assess the visibility of normal and abnormal A2 pulleys and the presence of motion or ghost artefacts. RESULTS: Normal and abnormal A2 pulleys were visible in 94% (59/63) and 95% (60/63) on T1WI sequences, in 63% (40/63) and 60% (38/63) on FS T2WI sequences, and in 87% (55/63) and 73% (46/63) on Gd FS T1WI sequences when read by the first and second observer, respectively. Motion and ghost artefacts were higher on FS T2WI sequences. Seven among eight abnormal A2 pulleys were detected, and were best depicted with Gd FS T1WI sequences in 71% (5/7) and 86% (6/7) by the first and the second observer, respectively. CONCLUSION: In 3-T MRI, the comparison between transverse T1WI, FS T2WI, and Gd FS T1WI sequences shows that transverse T1WI allows excellent depiction of the A2 pulley, that FS T2WI suffers from a higher rate of motion and ghost artefacts, and transverse Gd FS T1WI is the best sequence for the depiction of abnormal A2 pulley.

Differences in whole-body fat oxidation kinetics between cycling and running.

This study aimed to quantitatively describe and compare whole-body fat oxidation kinetics in cycling and running using a sinusoidal mathematical model (SIN). Thirteen moderately trained individuals (7 men and 6 women) performed two graded exercise tests, with 3-min stages and 1 km h(-1) (or 20 W) increment, on a treadmill and on a cycle ergometer. Fat oxidation rates were determined using indirect calorimetry and plotted as a function of exercise intensity. The SIN model, which includes three independent variables (dilatation, symmetry and translation) that account for main quantitative characteristics of kinetics, provided a mathematical description of fat oxidation kinetics and allowed for determination of the intensity (Fat(max)) that elicits maximal fat oxidation (MFO). While the mean fat oxidation kinetics in cycling formed a symmetric parabolic curve, the mean kinetics during running was characterized by a greater dilatation (i.e., widening of the curve, P < 0.001) and a rightward asymmetry (i.e., shift of the peak of the curve to higher intensities, P = 0.01). Fat(max) was significantly higher in running compared with cycling (P < 0.001), whereas MFO was not significantly different between modes of exercise (P = 0.36). This study showed that the whole-body fat oxidation kinetics during running was characterized by a greater dilatation and a rightward asymmetry compared with cycling. The greater dilatation may be mainly related to the larger muscle mass involved in running while the rightward asymmetry may be induced by the specific type of muscle contraction.

Determinants of basal fat oxidation in healthy Caucasians.

In a retrospective study, we examined several determinants of basal fat oxidation in 720 healthy Caucasian volunteers. Adult men (n = 427) and women (n = 293) were characterized for resting energy expenditure and substrate oxidation by indirect calorimetry (after a 12-h overnight fast), peak O2 consumption by a treadmill test to exhaustion, body composition by hydrodensitometry, food intake from a 3-day food diary, and hormonal status by fasting hormone concentrations. Fat oxidation was negatively correlated with fat mass in men (r = -0.11; P < 0.05), but no statistical relationship was found in women. In a stepwise multiple regression analysis, fat oxidation was best predicted by peak O2 consumption and fat-free mass in men (model R2 = 0.142) and by free thyroxine, fat-free mass, and fasting insulin in women (model R2 = 0.153). Relative rates of fat oxidation (fat oxidation adjusted for differences in resting energy expenditure) were not correlated with fat mass in either gender. Women showed a lower rate of basal fat oxidation (both absolute and adjusted) than did men. Our results show that fat oxidation is not greater in individuals with a greater fat mass. Furthermore, our results support a sexual dimorphism in basal rates of fat oxidation.

Fat intake and adiposity in 8 to 11-year-old obese children.

OBJECTIVE: To investigate the relationships between diet composition, body composition, and macronutrient oxidation at rest in obese and non-obese children. DESIGN: Cross-sectional study on fat intake, adiposity and postabsorptive macronutrients oxidation rates. SUBJECTS: 82 prepubertal (age: 9.1 +/- 1.1 y) children, 30 obese (FM = 32.6 +/- 6.1%) and 52 non-obese (FM = 15.6 +/- 5.1%). MEASUREMENTS: Subcutaneous skinfold thickness for body composition, diet history for energy and nutrient intake, indirect calorimetry for resting metabolic rate (RMR) and RQ measurement. RESULTS: Energy intake (EI) was comparable in obese and non-obese children. Adjusted for RMR by ANCOVA, using RMR as the covariate, EI was significantly lower in obese than in non-obese children indicating either a blunted physical activity or a systematic underestimation of EI. Protein and carbohydrate intakes expressed as a percentage of total energy intake (%EI) were not significantly different in the two groups. Lipid intake (%EI) was slightly but significantly higher in the obese than in the non-obese group either unadjusted or adjusted for RMR by ANCOVA. The postabsorptive RQ was significantly lower in obese than in non-obese children. In the total group, %FM was weakly but significantly correlated to lipid intake (%EI). CONCLUSION: Obese prepubertal children have a higher relative fat intake than non-obese children and their FM is associated with this factor. The lower postabsorptive RQ of obese children may indicate a compensatory mechanism to achieve fat equilibrium by enhanced fat oxidation.

Reproducibility and within-day variability of body fat measurements using segmental bipolar bioelectrical impedance in women

BACKGROUND AND AIMS: little is known regarding the reproducibility of body fat measuring devices; hence, we assessed the between and within-device reproducibility, and the within-day variability of body fat measurements. METHODS: body fat percentage was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 ± 2.5 kg/m2 (mean ± SD) using seven bipolar bioelectrical impedance devices. Each participant was also measured each hour between 7:00 and 22:00. RESULTS: the correlation between first and second measurements was very high (Spearman r between 0.985 and 1.000, p<0.001), as well as between devices (Spearman r between 0.916 and 0.991, p<0.001). Repeated measurements analysis showed no differences were between devices (p=0.59) or readings (first vs. second: p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon (F test for repeated values= 6.58, p<0.001). CONCLUSIONS: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.