Short-term isocaloric manipulation of carbohydrate intake: effect on subsequent ad libitum energy intake.
ABSTRACT: BACKGROUND:Isocaloric manipulation of carbohydrate or fat intake could alter subsequent ad libitum food intake. METHODS:In a controlled inpatient study, we investigated whether isocaloric manipulation of carbohydrate or fat would alter subsequent ad libitum energy intake. Eighteen non-diabetic subjects (age range 19-53 years.; 15 M/3F; % body fat 38.5 ± 9.1 (mean ± SD)) were fed for 3 days an isocaloric high-carbohydrate diet (HC; 60% carbohydrate, 20% fat, 20% protein) and a high-fat diet (HF; 50% fat, 30% carbohydrate, 20% protein) in random order each followed by 3 days of ad libitum food intake. RESULTS:There were no differences in mean daily energy intake (EI) following each diet (HC vs. HF: 4,811 ± 1,190 vs. 4,823 ± 1,238 kcal/d; P = 0.7) or in the percent of weight maintenance energy needs (%EN-WM; 173 ± 41 vs. 173 ± 46%, P = 0.5). However, the individual difference in EI between the HF versus HC diet (?EI) both on day one and over the 3 days of each ad libitum period was negatively associated with % body fat (%BF) and waist circumference (day 1: ?EI vs. %BF, r = -0.49, P = 0.04; mean day 1-3 kcal ?EI vs. %BF, r = -0.66, P = 0.003, and ?EI vs. waist, r = -0.65, P = 0.004). CONCLUSIONS:A short-term isocaloric HC diet did not result in overall lower EI compared with a HF diet in the same individuals. However, we did find that increasing body fat was associated with less decline in EI following the HC versus HF diet indicating that increasing adiposity is associated with altered regulation of EI in response to macronutrient changes.
Project description:To evaluate the effects of overeating (140% of energy requirements) a high-fat low-energy density diet (HF/LED, 1.05 kcal/g), high-fat high-energy density diet (HF/HED, 1.60 kcal/g), and high-carbohydrate (HC) LED (1.05 kcal/g) for 2-days on subsequent 4-day energy intake (EI), activity levels, appetite, and mood.Using a randomized cross-over design, energy expenditure and EI were standardized during overeating.In 20 adults with a mean ± SD BMI of 30.7 ± 4.6 kg/m(2) , EI was not suppressed until the second day after overeating and accounted for ?30% of the excess EI. Reductions in EI did not differ among the three diets or across days. Overeating had no effect on subsequent energy expenditure but steps/day decreased after the HC/LED and HF/HED. Sleep time was increased after the HF/HED compared to both LEDs. After overeating a HF/HED vs. HF/LED, carbohydrate cravings, hunger, prospective food consumption, and sadness increased and satisfaction, relaxation, and tranquility decreased.Diet type, time, or their interaction had no impact on compensation over 4 days. No adaptive thermogenesis was observed. The HF/HED vs. HF/LED had detrimental effects on food cravings, appetite, and mood. These results suggest short-term overeating is associated with incomplete compensation.
Project description:BACKGROUND:Broiler chickens are compulsive feeders that become obese as juveniles and are thus a unique model for metabolic disorders in humans. However, little is known about the relationship between dietary composition, fasting and refeeding and adipose tissue physiology in chicks. Our objective was to determine how dietary macronutrient composition and fasting and refeeding affect chick adipose physiology during the early post-hatch period. METHODS:Chicks were fed one of three isocaloric diets after hatch: high-carbohydrate (HC; control), high-fat (HF; 30% of ME from soybean oil) or high-protein (HP; 25% vs. 22% crude protein). At 4 days post-hatch, chicks were fed (continuous ad libitum access to food), fasted (3 h food withdrawal), or refed (fasted for 3 h and refed for 1 h). Subcutaneous, clavicular, and abdominal adipose tissue was collected for histological analysis and to measure gene expression, and plasma to measure non-esterified fatty acid (NEFA) concentrations (n?=?6-10 per group). RESULTS:Adipose tissue weights were reduced in chicks that were fed the HP diet and adipocyte diameter was greater in the adipose tissue of chicks that ate the HF diet. Consumption of diets differing in protein and fat content also affected gene expression; mRNAs encoding fatty acid binding protein 4 and a lipolytic enzyme, monoglyceride lipase, were greater in chicks fed the HC and HF than HP diet in all three adipose tissue depots. Fasting influenced gene expression in a depot-dependent manner, where most fasting and refeeding-induced changes were observed in the clavicular fat of chicks that consumed the HC diet. Fasting increased plasma NEFA concentrations in chicks fed the HC and HP diets. CONCLUSIONS:The decreased adipose tissue deposition in chicks fed the HP diet is likely explained by decreased rates of adipogenesis. Consumption of the HF diet was associated with greater adipose tissue deposition and larger adipocytes, likely as a result of greater rates of adipocyte hypertrophy. The depot-dependent effects of diet and fasting on gene expression may help explain mechanisms underlying metabolic distinctions among subcutaneous and visceral fat depots in humans.
Project description:Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition.In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983.Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group.Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease.Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.
Project description:The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids.Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal.There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (?6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ? 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (?19%; P ? 0.01) on the CHOICE diet.This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.
Project description:<h4>Objective</h4>This study aimed to compare self-reported with objective measurements of energy intake changes (?EI) during a 1-year weight-loss intervention with subjects randomized to low-carbohydrate versus low-fat diets.<h4>Methods</h4>Repeated body weight measurements were used as inputs to an objective mathematical model to calculate ?EI<sub>Model</sub> and to compare with self-reported energy intake changes assessed by repeated 24-hour recalls (?EI<sub>Recall</sub> ).<h4>Results</h4>?EI<sub>Recall</sub> indicated a relatively persistent state of calorie restriction of ~500 to 600 kcal/d at 3, 6, and 12 months with no significant differences between the diets. ?EI<sub>Model</sub> demonstrated large early decreases in calorie intake > 800 kcal/d followed by an exponential return to ~100 kcal/d below baseline at the end of the year. Accounting for self-reported physical activities did not materially affect the results. Discrepancies between ?EI<sub>Model</sub> and ?EI<sub>Recall</sub> became progressively greater over time. The low-carbohydrate diet resulted in ?EI<sub>Model</sub> that was 162 ± 53 kcal/d lower than the low-fat diet over the first 3 months (P? = ?0.002), but no significant diet differences were found thereafter.<h4>Conclusions</h4>Self-reported ?EI measurements were inaccurate. Model-based calculations of ?EI found that instructions to follow the low-carbohydrate diet resulted in greater calorie restriction than the low-fat diet in the early phases of the intervention, but these diet differences were not sustained.
Project description:In the development of obesity, the source of excess energy may influence appetite and metabolism. To determine the effects of differences in diet composition in obesity, mice were fed either a high-carbohydrate diet (HC; 10% fat energy) or a high-fat energy-restricted diet (HFR; 60% fat energy) over 18 wk in weight-matched groups of mice. To identify obesity-associated genes with persistently altered expression following weight reduction, mice were fed either a standard low-fat diet (LF; 10% fat energy), an unrestricted high-fat diet (HF; 60% fat energy), or a HF diet followed by weight reduction (WR). Mice fed a HF diet had significantly greater gonadal fat mass and higher whole blood glucose concentrations than mice fed an HC diet. Of the mice fed a high-fat diet, total body weight and serum insulin concentrations were greater in HF than in HFR. Microarray analysis revealed that HF vs. HC feeding resulted in global differences in adipocyte gene expression patterns. Although we identified genes whose expression was altered in both moderately and severely obese mice, there were also a large number of genes with altered expression only in severe obesity. Formerly obese, WR mice did not differ significantly from lean controls in total body weight or physiological measures. However, microarray analysis revealed distinctly different patterns of adipocyte gene expression. Furthermore, there were 398 genes with altered expression in HF mice that persisted in WR mice. Genes with persistently altered expression following obesity may play a role in rebound weight gain following weight reduction.
Project description:<h4>Background</h4>Low-carbohydrate diets are suggested to exert metabolic benefits by reducing circulating triacylglycerol (TG) concentrations, possibly by enhancing mitochondrial activity.<h4>Objective</h4>We aimed to elucidate mechanisms by which dietary carbohydrate and fat differentially affect hepatic and circulating TG, and how these mechanisms relate to fatty acid composition.<h4>Methods</h4>Six-week-old, ∼300 g male Wistar rats were fed a high-carbohydrate, low-fat [HC; 61.3% of energy (E%) carbohydrate] or a low-carbohydrate, high-fat (HF; 63.5 E% fat) diet for 4 wk. Parameters of lipid metabolism and mitochondrial function were measured in plasma and liver, with fatty acid composition (GC), high-energy phosphates (HPLC), carnitine metabolites (HPLC-MS/MS), and hepatic gene expression (qPCR) as main outcomes.<h4>Results</h4>In HC-fed rats, plasma TG was double and hepatic TG 27% of that in HF-fed rats. The proportion of oleic acid (18:1n-9) was 60% higher after HF vs. HC feeding while the proportion of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7), and estimated activities of stearoyl-CoA desaturase, SCD-16 (16:1n-7/16:0), and de novo lipogenesis (16:0/18:2n-6) were 1.5-7.5-fold in HC vs. HF-fed rats. Accordingly, hepatic expression of fatty acid synthase (Fasn) and acetyl-CoA carboxylase (Acaca/Acc) was strongly upregulated after HC feeding, accompanied with 8-fold higher FAS activity and doubled ACC activity. There were no differences in expression of liver-specific biomarkers of mitochondrial biogenesis and activity (Cytc, Tfam, Cpt1, Cpt2, Ucp2, Hmgcs2); concentrations of ATP, AMP, and energy charge; plasma carnitine/acylcarnitine metabolites; or peroxisomal fatty acid oxidation.<h4>Conclusions</h4>In male Wistar rats, dietary carbohydrate was converted into specific fatty acids via hepatic lipogenesis, contributing to higher plasma TG and total fatty acids compared with high-fat feeding. In contrast, the high-fat, low-carbohydrate feeding increased hepatic fatty acid content, without affecting hepatic mitochondrial fatty acid oxidation.
Project description:The energy balance regulation may differ in lean and obese people. The purposes of our study were to evaluate the hormonal response to meals with varying macronutrient content, and the differences depending on body weight. METHODS:The crossover study included 46 men, 21?58 years old, normal-weight and overweight/obese. Every subject participated in two meal-challenge-tests with high-carbohydrate (HC), and normo-carbohydrate (NC) or high-fat (HF) meals. Fasting and postprandial blood was collected for a further 240 min, to determine adiponectin, leptin and total ghrelin concentrations. RESULTS:In normal-weight individuals after HC-meal we observed at 60min higher adiponectin concentrations (12,554 ± 1531 vs. 8691 ± 1070 ng/mL, p = 0.01) and significantly (p < 0.05) lower total ghrelin concentrations during the first 120 min, than after HF-meal intake. Fasting and postprandial leptin levels were significantly (p < 0.05) higher in overweigh/obese men. Leptin concentrations in normal-weight men were higher (2.72 ± 0.8 vs. 1.56 ± 0.4 ng/mL, p = 0.01) 180 min after HC-meal than after NC-meal intake. CONCLUSIONS:Our results suggest that in normal-body weight men we can expect more beneficial leptin, adiponectin, and total ghrelin response after HC-meal intake, whereas, in overweight/obese men, the HC-meal intake may exacerbate the feeling of hunger, and satiety may be induced more by meals with lower carbohydrate content.
Project description:<h4>Background</h4>The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood.<h4>Objective</h4>We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs).<h4>Methods</h4>In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z.<h4>Results</h4>Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable.<h4>Conclusion</h4>Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.
Project description:<h4>Objective</h4>The risks of excess sugar intake in addition to high-fat diet consumption on immunopathogenesis of obesity-associated metabolic diseases are poorly defined. Interleukin-4 (IL-4) and IL-13 signaling via IL-4Rα regulates adipose tissue lipolysis, insulin sensitivity, and liver fibrosis in obesity. However, the contribution of IL-4Rα to sugar rich diet-driven obesity and metabolic sequelae remains unknown.<h4>Methods</h4>WT, IL-4Rα-deficient (IL-4Rα<sup>-/-</sup>) and STAT6-deficient mice (STAT6<sup>-/-</sup>) male mice were fed low-fat chow, high fat (HF) or HF plus high carbohydrate (HC/fructose) diet (HF + HC). Analysis included quantification of: (i) body weight, adiposity, energy expenditure, fructose metabolism, fatty acid oxidation/synthesis, glucose dysmetabolism and hepatocellular damage; (ii) the contribution of the hematopoietic or non-hematopoietic IL-4Rα expression; and (iii) the relevance of IL-4Rα downstream canonical STAT6 signaling pathway in this setting.<h4>Results</h4>We show that IL-4Rα regulated HF + HC diet-driven weight gain, whole body adiposity, adipose tissue inflammatory gene expression, energy expenditure, locomotor activity, glucose metabolism, hepatic steatosis, hepatic inflammatory gene expression and hepatocellular damage. These effects were potentially, and in part, dependent on non-hematopoietic IL-4Rα expression but were independent of direct STAT6 activation. Mechanistically, hepatic ketohexokinase-A and C expression was dependent on IL-4Rα, as it was reduced in IL-4Rα-deficient mice. KHK activity was also affected by HF + HC dietary challenge. Further, reduced expression/activity of KHK in IL-4Rα mice had a significant effect on fatty acid oxidation and fatty acid synthesis pathways.<h4>Conclusion</h4>Our findings highlight potential contribution of non-hematopoietic IL-4Rα activation of a non-canonical signaling pathway that regulates the HF + HC diet-driven induction of obesity and severity of obesity-associated sequelae.