Self-selected meal composition alters the relationship between same-day caloric intake and appetite scores in humans during a long-term ad-libitum feeding study.

PURPOSE: To determine the effect of an off-protocol meal during a long-term ad libitum feeding study on changes in total caloric consumption and ratings of hunger and satiety. METHODS: During the ad libitum portion of a 16 weeks research high-protein feeding study, 19 participants were allowed to eat up to one self-selected meal (SSM) a week instead of an intervention diet meal. The SSM was assessed for total caloric and macronutrient composition and compared to the intervention diet for 3 days before and after the SSM day. Visual analog scores rating daily hunger and fullness were collected and compared as well. RESULTS: On the SSM day, the mean ± SD daily caloric intake increased by 262 ± 332 kcal compared to the previous study days (P < 0.001), with no changes in subjective appetite scores. The following day there was a slight but significant reduction in intake (- 58 ± 85 kcal, P = 0.008) compared to the average pre-SSM day with no change in appetite scores. On the SSM day, percent protein intake was inversely associated mean daily caloric intake (r2 = 0.22, P = 0.03). CONCLUSIONS: During a long-term, ad-libitum high-protein feeding study, one SSM lower in protein increased daily total caloric consumption with no impact on appetite ratings and incomplete caloric consumption during subsequent days. These data suggest that during ad-libitum feeding, a single meal change in protein content impacts the relationships between daily level of hunger, satiety and calorie intake. GOV ID: NCT05002491 (retrospectively registered 07/20/2021).

A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

PURPOSE: We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. METHODS: Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. RESULTS: The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high: LFD: 0.11 ± 0.37 vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p < 0.01; HFD: r = -0.71; p = 0.02). CONCLUSIONS: A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. GOV IDENTIFIER: NCT00930371.

No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial.

BACKGROUND: Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages (SSBs), likely mainly because of an inadequate satiety response to liquid calories. However, SSBs have a high content of fructose, the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis. It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs. OBJECTIVE: We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption. DESIGN: We conducted 2 randomized, controlled, double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose-, glucose-, or aspartame-sweetened beverage (study A; n = 9) or a fructose-, glucose-, or high-fructose corn syrup (HFCS)-sweetened beverage (study B; n = 24) for 8 d on overall energy intake. SSBs were provided at 25% of estimated energy requirement, or an equivalent volume of the aspartame-sweetened beverage, and consumption was mandatory. All solid foods were provided at 125% of estimated energy requirements and were consumed ad libitum. RESULTS: In study A, ad libitum energy intake was 120% ± 10%, 117% ± 12%, and 102% ± 15% of estimated energy requirements when subjects consumed the fructose-, glucose-, and aspartame-sweetened beverages. Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase (P < 0.003 for each), with no difference between the fructose and glucose phases (P = 0.462). In study B, total energy intake during the fructose, HFCS, and glucose phases was 116% ± 14%, 116% ± 16%, and 116% ± 16% of the subject's estimated total energy requirements (P = 0.880). CONCLUSIONS: In healthy adults, total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages. The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages. These trials were registered at clinicaltrials.gov as NCT00475475 and NCT01424306.

Effects of dietary fat and saturated fat content on liver fat and markers of oxidative stress in overweight/obese men and women under weight-stable conditions.

Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change -2.13% (-3.74%, -0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.

Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not ß-cell function in humans.

BACKGROUND: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. OBJECTIVE: The objective was to investigate whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. DESIGN: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess ß-cell function and hepatic and systemic insulin sensitivity. RESULTS: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with ß-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for ß-cell function. CONCLUSION: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat.

n3 PUFAs do not affect adipose tissue inflammation in overweight to moderately obese men and women.

Recent studies have indicated that omega-3 (n3) polyunsaturated fatty acids (PUFAs) decrease adipose tissue inflammation in rodents and in morbidly obese humans. We investigated whether a diet rich in n3 PUFAs from both marine and plant sources reduces adipose tissue and systemic inflammation in overweight to moderately obese adults. We conducted a randomized, single-blind, parallel-design, placebo-controlled feeding trial. Healthy men and women with a body mass index between 28 and 33 kg/m(2) consumed a diet rich in n3 PUFAs (3.5% of energy intake; n = 11) from plant and marine sources or a control diet (0.5% of energy intake from n3 PUFAs; n = 13). These diets were consumed for 14 wk (ad libitum for 12 wk). All foods were provided for the entire study period. Subcutaneous abdominal adipose tissue and fasting plasma were collected after the first 2 wk with the control diet and again at the end of the 14-wk dietary period. The primary outcome of this ex post analysis was the adipose tissue gene expression of 13 key mediators of inflammation. Adipose tissue gene expression of inflammatory mediators did not differ between the 2 groups, after adjustment for weight change. Furthermore, none of the 5 plasma markers of systemic inflammation differed significantly as an effect of diet treatment. We conclude that a relatively high dose of n3 PUFAs from plant and marine sources did not significantly lower adipose tissue or systemic inflammation in overweight to moderately obese healthy men and women over 14 wk.

Effects of a high-protein diet on regulation of phosphorus homeostasis.

CONTEXT: High-protein diets, which are popular for weight loss, contain large quantities of phosphorus. Phosphorus excess and consequent changes in phosphorus regulatory hormones are implicated in vascular calcification and cardiovascular disease. OBJECTIVE: We tested the hypothesis that a moderate increase in dietary phosphorus during a high-protein diet leads to changes in phosphorus-responsive hormones. DESIGN, PARTICIPANTS, AND SETTING: We conducted a post hoc analysis of a sequential dietary modification trial in 19 healthy volunteers in the general community. INTERVENTION: Participants received 2 weeks of a weight-maintaining, low-protein (15%) diet, followed by 2 weeks of an isocaloric, high-protein (30%) diet, followed by 12 weeks of an ad libitum high-protein (30%) diet. MAIN OUTCOME MEASURES: Using previously collected samples, plasma concentrations of fibroblast growth factor-23 (FGF-23), PTH, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D were measured at 8 time points to assess 24-hour variability and in 24-hour pooled samples to delineate changes at the end of each diet period. RESULTS: Mean dietary phosphorus intake during each study period was 1556, 2071, and 1622 mg/d, respectively. Plasma concentrations of FGF-23 and vitamin D metabolites varied in a diurnal pattern; plasma PTH concentrations varied in a bimodal pattern. After changing from a low- to high-protein isocaloric diet, plasma FGF-23 concentrations decreased slightly (mean -4.48 pg/mL, 95% confidence interval 1.88-7.07). There were no other statistically significant changes in phosphorus regulatory hormones in response to diet modifications. CONCLUSIONS: Among healthy people, an approximate 33% increase in dietary phosphorus after institution of a high-protein diet does not cause large changes in measured concentrations of phosphorus regulatory hormones.

Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum.

BACKGROUND: The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. METHODS: We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. RESULTS: Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations (P < 0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P < 0.001 for both).Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. CONCLUSIONS: Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.

Dietary n-3-polyunsaturated fatty acids and energy balance in overweight or moderately obese men and women: a randomized controlled trial.

BACKGROUND: Dietary n-3-polyunsaturated fatty acids (n-3-PUFA) have been shown to reduce body weight and fat mass in rodents as well as in humans in one small short-term study. We conducted this controlled randomized dietary trial to test the hypothesis that n-3-PUFA lower body weight and fat mass by reducing appetite and ad libitum food intake and/or by increasing energy expenditure. METHODS: Twenty-six overweight or moderately obese (body mass index 28-33 kg/m²) men and women were included, and received either a diet rich in n-3-PUFA from both plant and marine sources or a control diet. Diets were administered in an isocaloric fashion for 2 weeks followed by 12 weeks of ad libitum intake. The n-3-PUFA and control diets were identical in all regards except for the fatty acid composition. All foods were provided to subjects, and leftovers were weighed back to assess actual food intake accurately for each day of the study. This design gave us 80% power to detect a difference in weight change between the n-3-PUFA and control diet groups of 2.25 kg at an α-error level of 5%. RESULTS: Both groups lost similar amounts of weight when these diets were consumed ad libitum for 12 weeks [mean (SD): -3.5 (3.7) kg in the control group vs. -2.8 (3.7) kg in the n-3-PUFA group, F(1,24) = 13.425, p = 0.001 for time effect; F(1,24) = 0.385, p = 0.541 for time x group interaction]. Consistent with this finding, we also found no differences between the n-3-PUFA and control groups with regard to appetite as measured by visual analogue scale, ad libitum food intake, resting energy expenditure as measured by indirect calorimetry, diurnal plasma leptin concentrations, or fasting ghrelin concentrations. CONCLUSION: Our results suggest that dietary n-3-PUFA do not play an important role in the regulation of food intake, energy expenditure, or body weight in humans.

Effect of dietary n-3 polyunsaturated fatty acids on plasma total and high-molecular-weight adiponectin concentrations in overweight to moderately obese men and women.

BACKGROUND: Recent studies indicated that dietary n-3 polyunsaturated fatty acids (PUFAs) increase circulating adiponectin concentrations in rodents. OBJECTIVE: We aimed to investigate whether a diet rich in n-3 PUFAs increased plasma concentrations of total or high-molecular-weight (HMW) adiponectin in healthy overweight-to-moderately obese men and women. DESIGN: Sixteen women and 10 men with a body mass index (in kg/m(2)) between 28 and 33 were randomly assigned to consume a diet rich in n-3 PUFAs (3.5% of energy intake) from both plant and marine sources or a control diet (0.5% of energy intake from n-3 PUFAs). For the first 2 wk, these diets were consumed under isocaloric conditions; then followed a 12-wk period of ad libitum consumption that was associated with a moderate loss of approximately 3.5% of body weight in both groups. Total and HMW adiponectin plasma concentrations were measured before and after each diet phase. RESULTS: Plasma fasting adiponectin concentrations did not change during the isocaloric period, but they increased modestly ( approximately 10%) during the ad libitum period when subjects lost weight [P = 0.009 for time in repeated-measures analysis of variance] and to a similar extent in subjects consuming the control (x +/- SD: 0.42 +/- 0.69 microg/mL) and n-3 PUFA (0.45 +/- 0.85 microg/mL) diets (P = 0.920 for time x treatment interaction). Plasma concentrations of HMW adiponectin did not change significantly during the study. CONCLUSION: Dietary n-3 PUFAs consumed at levels of 3.5% of energy intake do not significantly increase plasma or HMW adiponectin concentrations in overweight-to-moderately obese healthy men and women over the course of 14 wk.

Association of cognitive restraint with ghrelin, leptin, and insulin levels in subjects who are not weight-reduced.

Despite widespread efforts at weight loss, the prevalence of obesity continues to rise. Restrained eating is a pattern of attempted weight control characterized by cognitive restriction of food intake that has paradoxically been linked with overeating and/or weight gain. It is not known whether restrained eating is associated with abnormalities in appetite-regulating hormones, independent of its effects on body weight. To address this question, we assessed cognitive restraint using the Three-Factor Eating Questionnaire and obtained fasting measurements of ghrelin, leptin and insulin from 24 healthy, non-obese (body mass index (BMI) 19.7 to 29.6 kg/m(2)) adult subjects who were at a stable, lifetime maximum weight. We chose to study subjects at stable maximum weight to avoid the secondary effects of weight reduction on body-weight regulating hormones. Subjects were classified by cognitive restraint scale score into Low, Indeterminate, and High Restraint groups. Higher ghrelin levels were significantly associated with restraint in an unadjusted model (P=0.004) and after adjustment for BMI (P=0.007). No relationships were found between restraint scores and either leptin (P=0.75) or insulin (P=0.36). These findings show an orexigenic hormonal profile in restrained eaters, independent of changes in body weight.

Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates.

CONTEXT: Ghrelin is an orexigenic hormone that can increase body weight. Its circulating levels increase before meals and are suppressed after food ingestion. Understanding the effects of specific types of ingested macronutrients on ghrelin regulation could facilitate the design of weight-reducing diets. OBJECTIVE: We sought to understand how ingestion of carbohydrates, proteins, or lipids affect acyl (bioactive) and total ghrelin levels among human subjects, hypothesizing that lipids might suppress ghrelin levels less effectively than do either carbohydrates or proteins. DESIGN: This was a randomized, within-subjects cross-over study. SETTING: The study was conducted at a University Clinical Research Center. PARTICIPANTS: There were 16 healthy human subjects included in the study. INTERVENTIONS: Isocaloric, isovolemic beverages composed primarily of carbohydrates, proteins, or lipids were provided. MAIN OUTCOME MEASURES: The magnitude of postprandial suppression of total and acyl ghrelin levels (measured with a novel acyl-selective, two-site ELISA) was determined. RESULTS: All beverages suppressed plasma acyl and total ghrelin levels. A significant effect of macronutrient class on decremental area under the curve for both acyl and total ghrelin was observed; the rank order for magnitude of suppression was protein more than carbohydrate more than lipid. Total ghrelin nadir levels were significantly lower after both carbohydrate and protein, compared with lipid beverages. In the first 3 postprandial hours, the rank order for acyl and total ghrelin suppression was carbohydrate more than protein more than lipid. In the subsequent 3 h, there was a marked rebound above preprandial values of acyl and total ghrelin after carbohydrate ingestion alone. CONCLUSIONS: These findings suggest possible mechanisms contributing to the effects of high-protein/low-carbohydrate diets to promote weight loss, and high-fat diets to promote weight gain.

Changes in plasma amino Acid levels do not predict satiety and weight loss on diets with modified macronutrient composition.

OBJECTIVE: Serotonin mediates satiety in the central nervous system. Brain serotonin content depends on the plasma ratio of tryptophan (Trp) to large neutral amino acids (LNAA) and may be affected by diet composition. We examined whether high-carbohydrate or high-protein diets induce satiety and weight loss by altering plasma concentrations of these amino acids. METHODS: In study 1 (n = 16, BMI = 27.0 +/- 2.3), we compared plasma Trp and LNAA concentrations averaged over 24 h after 2 weeks of consuming isocaloric diets containing either 45 or 65% of total energy as carbohydrate. In study 2 (n = 19, BMI = 26.2 +/- 2.1), we made the same measurements following diets containing either 15 or 30% of total energy as protein. To assess satiety in both studies, we recorded caloric intake and weight changes during a subsequent 12-week period of ad libitum consumption of the experimental diets. RESULTS: Ad libitum caloric intake fell by 222 +/- 81 kcal/day with a 3.7 +/- 0.6 kg weight loss at 12 weeks in study 1. Ad libitum caloric intake fell by 441 +/- 63 kcal/ day with a 4.9 +/- 0.5 kg weight loss at 12 weeks in study 2. The 24-hour averaged plasma concentration of Trp and the Trp:LNAA ratio were unaffected by the isocaloric increase in carbohydrate or protein consumption that preceded the ad libitum administration of the 2 diets. CONCLUSION: An increase in either carbohydrate or protein intake increases satiety and leads to significant weight loss, however, these effects are not mediated by an increase in plasma concentration of Trp or the Trp:LNAA ratio.

Effect of aging on the response of ghrelin to acute weight loss.

OBJECTIVES: To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons. DESIGN: Prospective diet intervention study. SETTING: University of Washington Medical Center from 2001 through 2005. PARTICIPANTS: Twenty-one younger (18-35) and 18 older (> or =70) men and women. INTERVENTION: Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake. MEASUREMENTS: Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured. RESULTS: Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed. CONCLUSION: Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

Plasma C-reactive protein concentration is not affected by isocaloric dietary fat reduction.

OBJECTIVE: There is a strong correlation between plasma C-reactive protein (CRP) concentration and risk of cardiovascular death. Low-fat diets have been recommended for maintenance of cardiovascular health, and it is known that a low-fat diet associated with weight loss lowers CRP concentration. However, it remains unclear whether dietary fat has an effect independent from weight change on markers of inflammation. METHODS: Sixteen overweight subjects who were 46 +/- 14 y old were placed on a weight-maintaining baseline diet consisting of 35% fat, 45% carbohydrate, and 20% energy as protein. After 2 wk, subjects were switched to an isocaloric low-fat diet consisting of 15% fat, 65% carbohydrate, and 20% protein for another 2 wk. For the final 12 wk of the study, subjects consumed the same 15% fat diet ad libitum. At the end of each diet phase, CRP was measured by a high-sensitivity CRP assay. RESULTS: The weight of subjects remained stable during the first 4 wk of isocaloric diets. Plasma CRP concentrations after 2 wk on the weight-maintaining 35% fat diet and 2 wk on the isocaloric 15% fat diet were not significantly different (median +/- interquartile range 1.42 +/- 3.30 and 1.59 +/- 3.29 mg/L, respectively). Three months of ad libitum low-fat diet consumption resulted in a 4.1 +/- 0.7 kg weight loss associated with a decrease in CRP concentration to 1.17 +/- 2.03 mg/L (P = 0.03). CONCLUSION: Loss of body weight decreases CRP concentration, but a decrease in dietary fat without a concurrent change in body weight does not affect CRP concentration in overweight healthy subjects.

A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations.

BACKGROUND: Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake. OBJECTIVE: We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake. DESIGN: Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin. RESULTS: Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (+/-SE) spontaneous energy intake decreased by 441 +/- 63 kcal/d, body weight decreased by 4.9 +/- 0.5 kg, and fat mass decreased by 3.7 +/- 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC. CONCLUSIONS: An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.

A reduced-fat diet and aerobic exercise in Japanese Americans with impaired glucose tolerance decreases intra-abdominal fat and improves insulin sensitivity but not beta-cell function.

Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin sensitivity and the acute insulin response to glucose (AIRg) in 62 Japanese Americans (age 56.5 +/- 1.3 years; mean +/- SE) with impaired glucose tolerance (IGT) who were randomized to the American Heart Association (AHA) Step 2 diet plus endurance exercise (n = 30) versus the AHA Step 1 diet plus stretching (n = 32) for 24 months. beta-Cell function (disposition index [DI]) was calculated as S(i) x AIRg, where S(i) is the insulin sensitivity index. The incremental area under the curve for glucose (incAUCg) was calculated from a 75-g oral glucose tolerance test. Intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were measured by computed tomography. At 24 months, the Step 2/endurance group had lower weight (63.1 +/- 2.4 vs. 71.3 +/- 2.9 kg; P = 0.004) and IAF (75.0 +/- 7.9 vs. 112.7 +/- 10.4 cm(2); P = 0.03) and SCF (196.5 +/- 18.0 vs. 227.7 +/- 19.9 cm(2); P < 0.001) areas, greater S(i) (4.7 +/- 0.5 vs. 3.3 +/- 0.3 x 10(-5) min . pmol(-1) . l(-1); P = 0.01), and a trend toward lower AIRg (294.9 +/- 50.0 vs. 305.4 +/- 30.0 pmol/l; P = 0.06) and incAUCg (8,217.3 +/- 350.7 vs. 8,902.0 +/- 367.2 mg . dl(-1) . 2 h(-1); P = 0.08) compared with the Step 1/stretching group after adjusting for baseline values. There was no difference in the DI (P = 0.7) between the groups. S(i) was associated with changes in weight (r = -0.426, P = 0.001) and IAF (r = -0.395, P = 0.003) and SCF (r = -0.341, P = 0.01) areas. Thus, the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT. However, such changes did not improve beta-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term.

Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans.

Plasma ghrelin levels rise before meals and fall rapidly afterward. If ghrelin is a physiological meal-initiation signal, then a large oral caloric load should suppress ghrelin levels more than a small caloric load, and the request for a subsequent meal should be predicted by recovery of the plasma ghrelin level. To test this hypothesis, 10 volunteers were given, at three separate sessions, liquid meals (preloads) with widely varied caloric content (7.5%, 16%, or 33% of total daily energy expenditure) but equivalent volume. Preloads were consumed at 0900 h, and blood was sampled every 20 min from 0800 h until 80 min after subjects spontaneously requested a meal. The mean (+/- SE) intervals between ingestion of the 7.5%, 16%, and 33% preloads and the subsequent voluntary meal requests were 247 +/- 24, 286 +/- 20, and 321 +/- 27 min, respectively (P = 0.015), and the nadir plasma ghrelin levels were 80.2 +/- 2.8%, 72.7 +/- 2.7%, and 60.8 +/- 2.7% of baseline (the 0900 h value), respectively (P < 0.001). A Cox regression analysis failed to show a relationship between ghrelin profile and the spontaneous meal request. We conclude that the depth of postprandial ghrelin suppression is proportional to ingested caloric load but that recovery of plasma ghrelin is not a critical determinant of intermeal interval.

Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet.

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 +/- 57 vs. 580 +/- 56 ng/ml.24 h; P = NS). Body weight decreased from 74.6 +/- 2.4 to 70.8 +/- 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.