Hypocaloric Diet In Obese Subjects Research Articles

Effect of a Mediterranean-pattern diet on the metabolic response secondary to weight loss; role of the single nucleotide polymorphism (rs16147) of neuropeptide Y

Background and aims: intervention studies that evaluate the effect of rs16147 on metabolic response and weight change after dietary intervention are scarce. We propose to evaluate the role of the rs16147 genetic variant in the metabolic effects produced by a hypocaloric Mediterranean-pattern diet with high content of omega-9. Material and methods: a sample of 363 obese subjects was recruited. At the baseline visit the patients were randomly assigned to one of two hypocaloric diets for 12 weeks (diet M, Mediterranean pattern; diet C, standard hypocaloric). All patients, at baseline and at 12 weeks, had biochemical and anthropometric variables measured, and genotyping performed for the rs16147 variant. Results: in all subjects, and with both diets, the parameters of adiposity, blood pressure, and circulating leptin improved. In obese subjects with allele (A) insulin levels (GG vs. GA + AA) (-0.9 ± 1.1 IU/L vs. -4.4 ± 1.0 IU/L; p = 0.01) and HOMA-IR (-0.3 ± 0.1 units vs. -1.2 ± 0.3 units; p = 0.02) decreased significantly with diet M. Subjects carrying the minor allele showed a significant decrease in basal insulin levels (GG vs. GA + AA) (0.7 ± 0.3 IU/L vs. -2.2 ± 0.9 IU/L: p = 0.02) and HOMA-IR (-0.3 ± 0.2 units vs. -0.7 ± 0.1 units: p = 0.01) after diet C. This decrease in circulating insulin and HOMA-IR levels in patients with allele A was significantly higher with diet M than with diet C. Conclusions: the A allele of the rs16147 variant produces a better metabolic response in terms of insulin resistance and basal insulin secondary to weight loss with two different hypocaloric diets in obese subjects, with improvement being higher with the Mediterranean diet.

Increased fiber intake predicts the decrease in 2nd phase glucose-induced hyperinsulinemia following a hypocaloric diet in obese subjects

Background and aimsHigher fiber intake is associated with increased insulin sensitivity (IS) and reduced glucose-induced insulin secretion (GIIS) during isocaloric-diets; however, its role in hypocaloric-diets is unclear. We examined whether increased fiber intake predicts the amelioration in IS and GIIS following a hypocaloric-diet. Methods and resultsThis is a post-hoc analysis of 55 adult subjects (BMI > 27 kg/m2) who completed a 6-month hypocaloric-diet (−500 kcal/day). Dietary intake was assessed using 3-day food records at baseline and post-intervention. We evaluated glucose-induced insulin and C-peptide secretions as AUC of plasma insulin and C-peptide during intravenous-glucose-tolerance tests (IVGTT) and IS via hyperinsulinemic-euglycemic clamps. Data analysis employed regression models and 2-way RM ANOVAs. Post-intervention % change in fiber intake was associated positively with ISclamp (r = 0.30) and negatively with % change in total (r = −0.37) and 2nd phase GIISIVGTT (r = −0.44) but not C-peptide secretion. It remained associated with lower 2nd phase GIISIVGTT after adjustment for sex and % changes in BMI and energy-intake, independently of other macronutrients. Subjects who increased fiber intake (to 28.7 ± 9.0 g/day) had a greater decrease in 2nd phase GIISIVGTT, not C-peptide secretion, independently of sex or changes in adiposity or energy-intake compared to subjects who decreased intake (to 20.0 ± 6.8 g/day). ConclusionHigher fiber intake is an independent predictor of reduced 2nd phase glucose-induced hyperinsulinemia after a hypocaloric-diet. It was not associated with plasma C-peptide, suggesting a role in faster insulin clearance rather reduced insulin secretion. Promoting high-fiber intake may increase the effectiveness of hypocaloric-diets in preventing type 2 diabetes. RegistrationISRCTN14476404, BioMedCentral.com. Clinical trial registrationThis trial was registered at BioMed Central as ISRCTN14476404, on July 28th, 2017.

Impact of 2 Different Hypocaloric Diets on Serum Omentin Levels in Obese Subjects

Background and Aims: Omentin-1 might play a role in insulin resistance and obesity. This study is aimed at evaluating the influence of weight loss treatment on omentin-1 concentrations and other parameters after 2 different hypocaloric diets in obese subjects. Methods: A total of 239 obese subjects were randomly allocated during 12 weeks (Diet I – high-fat diet vs. Diet II – low fat diet), and their anthropometric and biochemical status were evaluated. Results: After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood, triglycerides, LDL cholesterol, insulin levels and homeostasis model assessment for insulin resistance decreased in a statistical manner from their base values. After consuming diet II (low fat diet), the omentin-1 levels increased in males (20 ± 14 ng/mL) and females (35 ± 19 ng/mL). No changes were observed in omentin-1 levels after consuming hypocaloric diet type I (high fat). The multiple regression analyses after weight loss with diet I adjusted by age and sex showed a statistical association between BMI kg/m² (Beta –0.33: 95% CI –4.58 to –0.11) and post-treatment omentin-1 levels. The analysis after weight loss with diet II showed a statistical association with BMI kg/m² (Beta –0.31: 95% CI –3.93 to –0.08) and insulin UI/L (Beta –0.25: 95% CI –4.63 to –0.05) with post-treatment omentin-1 levels. Conclusions: Our design showed a significant increase in serum omentin-1 levels after weight loss secondary to a low fat hypocaloric diet, in contrast to no changes following consuming a high fat hypocaloric diet.

Effect of the rs1862513 variant of resistin gene on insulin resistance and resistin levels after two hypocaloric diets with different fat distribution in subjects with obesity.

Polymorphisms of a single nucleotide in resistin gene (RETN) have been associated with insulin resistance. We decide to investigate the role of this polymorphism on insulin resistance and resistin levels after two hypocaloric diets. A sample of 361 obese non-diabetic Caucasian was enrolled. Biochemical evaluation and anthropometric data were measured at the start of the trial and repeated after 3 months of both diets (Diet P, Polyunsaturated vs. diet M, Monounsaturated). With both diets and in both genotype groups, BMI, weight, fat mass, waist circumference, systolic blood pressure, and diastolic blood pressure decreased. After diet P, insulin levels (GG vs. GC+CC genotypes) (-1.2±3.8 UI/L vs. -0.7±2.1 UI/L; p<0.05), HOMA-IR (-0.6±1.0 units vs. -0.4±0.9 units; p<0.05), total cholesterol (-10.5±20.1 mg/dl vs. -6.1±15.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.6±10.1 mg/dl vs. -2.2±9.1 mg/dl; p<0.05) decreased in subjects with GG genotype. After diet M, insulin levels (-1.8±2.1 UI/L vs. -0.6±3.0 UI/L: p>0.05), HOMA-IR (-0.5±1.0 units vs. -0.3±1.1 units: p>0.05), total cholesterol (-9.5±13.1 mg/dl vs. -4.4±8.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.1±6.1 mg/dl vs. -2.9±9.1 mg/dl; p<0.05) decreased, too. We suggest that GG genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, and LDL cholesterol secondary to two hypocaloric diet in obese subjects.

Effects of polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CB2R) on metabolic and adiposity parameters after weight loss with two hypocaloric diets

BackgroundThe role of CB2R gene variants on weight loss after a dietary intervention remained unclear. ObjectiveOur aim was to analyze the effects of rs3123554 of CB2R receptor gene on metabolic and adiposity parameters after two different hypocaloric diets in obese subjects. DesignA Caucasian population of 280 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet I – moderate in carbohydrate. Vs Diet II – normal in carbohydrate). ResultsIn both genotype groups (GG vs GA + AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet I and II. The decrease of these parameters was higher in non A allele carriers than A allele carriers. Pre- and post-dietary intervention, body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. In non A allele carriers, the decrease of glucose, insulin, HOMA-IR and Interleukin-6 levels was higher than A allele carriers after both diets. ConclusionCarriers of the minor allele of rs3123554 variant of CB2R gene loose less body weight during two different hypocaloric diets. The improvement of metabolic parameters was better in no A allele carriers than A allele carriers.

The association of SNP276G>T at adiponectin gene with insulin resistance and circulating adiponectin in response to two different hypocaloric diets

BackgroundSeveral adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. ObjectiveThe aim of our study was to analyze the effect of rs1501299 ADIPOQ gene polymorphism and dietary intake on total adiponectin levels and insulin resistance after two hypocaloric diets in obese subjects. Material and MethodsA Caucasian population of 284 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat). Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild) (dominant model). ResultsThe genotype distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased. Only in subjects with GG genotype, diet I and II decreased fasting insulin levels, HOMA-IR and adiponectin levels. The improvement was similar with both diets; insulin concentrations (Diet I: −4.7 ± 1.4 mUI/L vs. Diet II: −5.9 ± 1.9 mUI/L: p = .76), HOMA-IR (Diet I: −1.4 ± 0.6 units vs. Diet II: −2.0 ± 0.7 units: p = .56) and adiponectin levels (Diet I: −10.2 ± 3.4 ng/dl vs. Diet II: −14.0 ± 2.9 ng/dl: p = .33). ConclusionThe GG genotype of ADIPOQ gene variant (rs1501299) is associated with an increase in adiponectin levels and a decrease of insulin and HOMA-IR after weight loss.

Role of rs1501299 variant in the adiponectin gene on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet

Background/AimSeveral adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. Our aim was to analyze the effects of rs1501299 ADIPOQ gene polymorphism on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet in obese subjects. MethodsA Caucasian population of 82 obese patients was analyzed, before and after 3 months on a Mediterranean hypocaloric diet. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. ResultsAfter dietary treatment and in wild type group, weight, BMI, fat mass, leptin levels, systolic blood pressure and waist circumference decreases were similar to the mutant type group. In wild type group, the decrease in total cholesterol was −28.1 ± 15.3 mg/dl (mutant group: −12.6 ± 16.7 mg/dl:p = 0.009), LDL- cholesterol was −31.8 ± 20.5 mg/dl (−12.2 ± 11.5 mg/dl:p = 0.006), fasting glucose plasma −4.8 ± 2.5 mg/dL (−0.5 ± 0.1 mg/dL:p = 0.02), insulin −3.6 ± 1.5 mUI/L (+0.6 ± 1.1 mUI/L:p = 0.02) and HOMA-IR −1.2 ± 0.9 (−0.1 ± 1.1:p = 0.03). ConclusionThe present study suggests that T allele of ADIPO (rs1501299) could be a predictor of a lack of response of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a Mediterranean hypocaloric diet in obese subjects.

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

BackgroundRole of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients. ObjectiveOur aim was to analyze the effects of rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels after a standard hypocaloric diet in obese subjects. DesignA Caucasian population of 80 obese patients was analyzed before and after 3months on a standard hypocaloric diet. ResultsFifty patients (62.5%) had the genotype AA and 30 (37.5%) subjects had the next genotypes; AT (25 patients, 31.3%) or TT (5 study subjects, 6.3%) (second group). In non T allele carriers, the decreases in weight−3.4±2.9kg (T allele group −1.7±2.0kg:p=0.01), BMI −1.5±0.2kg (T allele group −1.2±0.5kg:p=0.02), fat mass−2.3±1.1kg (T allele group −1.7±0.9kg:p=0.009), waist circumference−3.8±2.4cm (T allele group −2.1±3.1cm:p=0.008), triglycerides −13.2±7.5mg/dl (T allele group +2.8±1.2mg/dl:p=0.02), insulin −2.1±1.9mUI/L (T allele group −0.3±1.0mUI/L:p=0.01), HOMA-IR −0.9±0.4 (T allele group −0.1±0.8:p=0.01) and leptin −10.1±9.5ng/dl (T allele group −3.1±0.2ng/dl:p=0.01) were higher than T allele carriers. Conclusionrs10767664 variant of BDNF gene modify anthropometric and biochemical changes after weight loss with a hypocaloric diet.

Polymorphism rs16147 of the Neuropeptide Y Gene Modifies the Response of Cardiovascular Risk Biomarkers and Adipokines to Two Hypocaloric Diets

Aims: Our aim was to evaluate the relationship of weight loss and changes in adipokine levels after two hypocaloric diets in obese subjects with polymorphism rs16147 of the neuropeptide Y gene. Subjects and Methods: A population of 283 obese patients was analyzed. At the basal visit, patients were randomly allocated to one of two diets for a period of 3 months (diet I, low in carbohydrates; diet II, low in fat). Results: With diet I and in both genotype groups (major versus minor allele), body mass index (BMI), weight, fat mass, waist circumference, and leptin decreased. With diet II and in all genotypes, BMI, weight, fat mass, waist circumference, and leptin decreased. With both diets and in subjects with the minor allele, insulin levels (diet I: major allele -1.7 ± 7.8 IU/L versus minor allele -4.2 ± 6.1 IU/L, p = 0.01; diet II: major allele -2.3 ± 6.1 IU/L versus minor allele -4.0 ± 5.2 IU/L, p = 0.02) and insulin resistance (diet I: major allele -0.2 ± 3.1 units versus minor allele -1.7 ± 3.0 units, p = 0.03; diet II: major allele -0.9 ± 2.0 units versus minor allele -1.7 ± 1.3 units, p = 0.01) decreased. Conclusion: The rs16147 genotype affected the reduction in insulin resistance and insulin levels in response to two different hypocaloric diets in obese subjects, with a lack of response in subjects with the major allele.

The rs1862513 Variant in Resistin Gene-Modified Insulin Resistance and Insulin Levels after Weight Loss Secondary to Hypocaloric Diet

Background/Aims: Polymorphisms of a single nucleotide in RETN have been associated with indexes of insulin resistance. Our aim was to analyze the effects of the rs1862513 RETN gene polymorphism on insulin resistance, insulin levels, and resistin levels changes after 3 months of a low-fat hypocaloric diet. Design: A Caucasian population of 133 obese patients was analyzed before and after 3 months on a low-fat hypocaloric diet. Results: Fifty-six patients (42.1%) had the genotype GG (wild group) and 77 (57.9%) patients had the other genotypes; GC (59 patients, 44.4%) or CC (18 patients, 13.5%; mutant group). In wild and mutant genotype groups, weight, body mass index, fat mass, waist circumference, and systolic blood pressure decreased. In the wild genotype group, the decrease in total cholesterol was -13.1 ± 25.3 mg/dL (vs. -4.4 ± 13.7 mg/dL in mutant group: p = 0.004 for group deltas), low density lipoprotein (LDL)-cholesterol was -13.0 ± 21.5 mg/dL (-4.3 ± 10.5 mg/dL: p = 0.007), glucose -7.2 ± 3.5 mg/dL (-0.8 ± 0.2 mg/dL: p = 0.01), insulin -5.6 ± 2.5 mUI/L (-2.9 ± 1.2 mUI/L: p = 0.03) and homeostasis model assessment-insulin resistance (HOMA-IR) -2.5 ± 1.1 (-0.6 ± 1.4: p = 0.02). Leptin levels decreased in both genotypes (-10.1 ± 9.5 ng/dL in wild type group vs. -13.1 ± 0.2 ng/dL in mutant type group: p > 0.05). Conclusion: The present study suggests that the G/G genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a hypocaloric diet in obese subjects.

Effect of high protein/very low carbohydrate diet and standard hypocaloric diet in obese subjects: Nutritional, biochemical and endothelial function evaluations

Effect of high protein/very low carbohydrate diet and standard hypocaloric diet in obese subjects: Nutritional, biochemical and endothelial function evaluations

Cardiovascular risk factors and adipocytokines levels after two hypocaloric diets with different fat distribution in obese subjects and rs6923761 gene variant of glucagon-like peptide 1 receptor.

The role of GLP-1 R variants on body weight response after dietary intervention is unclear. Our aim was to evaluate the effect of this polymorphism on cardiovascular risk factors, adipokine levels and weight loss secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets in obese subjects. 391 obese subjects were randomly allocated to one of these two diets for a period of 3 months; diet M (high monounsaturated fat hypocaloric diet) and diet P (high polyunsaturated (PUFAs) fat hypocaloric diet). Two hundred and twelve patients (54.2 %) had the genotype GG (wild group) and 179 (45.8 %) patients had the next genotypes; GA (146 patients, 37.3 %) or AA (33 patients, 8.7 %) (Mutant group). With both diets and in wild-type and mutant-type groups, BMI, weight, fat mass, waist circumference and systolic blood pressure decreased. Anthropometric parameters were higher in non-A-allele carriers than A-allele carriers. With both diets and in both genotypes, leptin, insulin levels and HOMA decreased. With the diet P and in wild genotype, total cholesterol and LDL-cholesterol levels decreased, too. Our data showed a lack of association of rs6923761 GLP-1 R polymorphism with weight loss after a high monounsaturated fat and a high polyunsaturated fat hypocaloric diets. Better anthropometric parameters in obese subjects with the mutant allele (A) of rs6923761 GLP-1 R polymorphism were observed. Insulin levels and HOMA decreased in non-A carriers.

Genetic Variation in the Beta 3-Adrenoreceptor Gene (Trp64Arg Polymorphism) and Its Influence on Anthropometric Parameters and Insulin Resistance Under a High Monounsaturated versus a High Polyunsaturated Fat Hypocaloric Diet

Objective: The aim of our study was to investigate the role of Trp64Arg polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene on metabolic changes and weight loss secondary to a high monounsaturated fat versus a high polyunsaturated fat hypocaloric diet in obese subjects. Material and Methods: A population of 260 obese subjects was analyzed. In the basal visit, patients were randomly allocated for 3 months to either diet M (high monounsaturated fat hypocaloric diet) or diet P (high polyunsaturated fat hypocaloric diet). Results: There were no significant differences between the positive effects (on weight, body mass index, waist circumference, fat mass) in either genotype group with both diets. With diet P and in genotype Trp64Trp, glucose levels (-6.7 ± 12.1 vs. -1.2 ± 2.2 mg/dl; p < 0.05), total cholesterol (-11.2 ± 8.1 vs. -1.0 ± 7.1 mg/dl; p < 0.05), low-density lipoprotein (LDL) cholesterol (-9.7 ± 10.1 vs. -2.2 ± 8.1 mg/dl; p < 0.05), triglycerides (-11.7 ± 13.1 vs. +1.7 ± 10.3 mg/dl; p < 0.05), homeostasis model assessment for insulin resistance (HOMA-R; -0.7 ± 1.1 vs. -0.3 ± 2.1 units; p < 0.05) and insulin levels (-1.8 ± 4.6 vs. -1.0 ± 9.1 mIU/l; p < 0.05) decreased. Conclusion: The metabolic effect of weight reduction by the two hypocaloric diets is greatest in subjects with the normal homozygous beta 3-AR gene. Improvements in total cholesterol, LDL cholesterol, triglyceride, glucose, insulin and HOMA-R levels were better than in the heterozygous group.

Role of G308 promoter variant of tumor necrosis factor alpha gene on weight loss and metabolic parameters after a high monounsaturated versus a high polyunsaturated fat hypocaloric diets

Background and objectiveThe aim of our study was to investigate the influence of G-308 promoter variant of the tumor necrosis factor (TNF) alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diet in obese subjects. Patients and methodA sample of 261 obese subjects were enrolled in a consecutive prospective way, from May 2011 to July 2012 in a tertiary hospital. In the basal visit, patients were randomly allocated during 3 months to Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). ResultsOne hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, body mass index (BMI), waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (−6.7(22.1)mg/dl vs −3.7(2.2)mg/dl: p=0.02), HOMA-R (−0.6(2.1)units vs −0.26(3.1)units: p=0.01), insulin levels (−1.7(6.6)UI/L vs −0.6(7.1)UI/L: p=0.009), total cholesterol levels (−15.3(31.1)mg/dl vs −8.4(22.1)mg/dl: p=0.01), LDL cholesterol levels (−10.7(28.1)mg/dl vs −3.8(21.1)mg/dl: p=0.008) and triglycerides (−12.1(52.1)mg/dl vs −6.6(43.1)mg/dl: p=0.02) decreased. ConclusionCarriers of the G-308G promoter variant of TNF alpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet.

Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets

An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.

Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1–4, and IGFBPs-1–3 protease activity in obese subjects

Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD). Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ). Free IGF-I was determined by a non-competitive immunoradiometric assay. Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups. We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.

Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity.

Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal IGFBP-1 levels and a decrease in basal insulin levels occurred in the normal controls, whereas no such changes were observed in the obese subjects. After caloric restriction 24-hr GH release, IGFBP-1 levels and insulin levels were similar in control subjects and obese subjects after weight loss. This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat and perpetuate the obese state.

Alanine flux in obese and healthy humans as evaluated by 15N- and 2H3-labeled alanines

Estimates of plasma alanine flux as measured in humans using L-[15N]-alanine or L-[3,3,3-2H3]alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocaloric diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the 2H tracer was two to three times greater than that obtained with [15N]alanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined.