Water Consumption Increases Weight Loss During a Hypocaloric Diet Intervention in Middle‐aged and Older Adults

Water consumption acutely reduces meal energy intake (EI) among middle‐aged and older adults. Our objectives were to determine if premeal water consumption facilitates weight loss among overweight/obese middle‐aged and older adults, and to determine if the ability of premeal water consumption to reduce meal EI is sustained after a 12‐week period of increased water consumption. Adults (n = 48; 55–75 years, BMI 25–40 kg/m²) were assigned to one of two groups: (i) hypocaloric diet + 500 ml water prior to each daily meal (water group), or (ii) hypocaloric diet alone (nonwater group). At baseline and week 12, each participant underwent two ad libitum test meals: (i) no preload (NP), and (ii) 500 ml water preload (WP). Meal EI was assessed at each test meal and body weight was assessed weekly for 12 weeks. Weight loss was ～2 kg greater in the water group than in the nonwater group, and the water group (β = ?0.87, P < 0.001) showed a 44% greater decline in weight over the 12 weeks than the nonwater group (β = ?0.60, P < 0.001). Test meal EI was lower in the WP than NP condition at baseline, but not at week 12 (baseline: WP 498 ± 25 kcal, NP 541 ± 27 kcal, P = 0.009; 12‐week: WP 480 ± 25 kcal, NP 506 ± 25 kcal, P = 0.069). Thus, when combined with a hypocaloric diet, consuming 500 ml water prior to each main meal leads to greater weight loss than a hypocaloric diet alone in middle‐aged and older adults. This may be due in part to an acute reduction in meal EI following water ingestion.     

Insulin Sensitivity in African‐American and White Women: Association With Inflammation

Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African‐American (n = 108) and white (n = 105) women, BMI 27–30 kg/m². Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual‐energy X‐ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)‐α, soluble tumor necrosis factor receptor (sTNFR)‐1, sTNFR‐2, C‐reactive protein (CRP), and interleukin (IL)‐6) with enzyme‐linked immunosorbent assay (ELISA). Whites had greater intra‐abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF‐α, sTNFR‐1, and sTNFR‐2 than African Americans. Greater TNF‐α in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = ?0.29 P < 0.05, and r = ?0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.     

Severely Obese Have Greater LPS‐stimulated TNF‐α Production Than Normal Weight African‐American Women

Obesity is associated with an increase in chronic, low‐grade inflammation which has been implicated in the development of type 2 diabetes mellitus and cardiovascular disease. The purpose of this study was to determine whether obesity was associated with an elevation of whole blood lipopolysaccharide (LPS)‐stimulated tumor necrosis factor‐α (TNF‐α) production. African‐American women were recruited from a larger study and assigned to one of five groups based on BMI: normal weight (NORM; BMI 20–25, n = 7), overweight (OVER; BMI 25–30, n = 12), class 1 obese (OB1; BMI 30–35, n = 19), class 2 obese (OB2; BMI 35–40, n = 10), or class 3 obese (OB3; BMI >40, n = 17). Body composition was determined via a whole body dual‐energy X‐ray absorptiometry (DXA) scan. Venous blood samples were collected following an overnight fast (>8 h), and stimulated with five doses of LPS (Salmonella enteriditis): 80, 40, 20, 10, and 5 µg/ml for 24 h in a 37 °C, 5% CO₂ incubator. Following stimulation, TNF‐α was measured using enzyme‐linked immunosorbent assay. OB3 produced 365% more TNF‐α than NORM at an LPS dose of 20 µg/ml (P < 0.05). When maximal TNF‐α production was assessed regardless of LPS dose, OB3 produced 230% more than NORM and OVER produced 190% more than NW (P = 0.001). Total and trunk fat mass and BMI were significantly correlated with maximal TNF‐α production and LPS = 20 µg/ml. Our findings are consistent with previous reports suggesting a relationship between increased adiposity and inflammatory marker production. This is one of the first studies to focus on African‐American women, who have higher rates of obesity.     

Epigenetic variation in OPRM1 gene in opioid‐exposed mother‐infant dyads

Neonatal abstinence syndrome (NAS) due to in‐utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ‐opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid‐exposed mother‐infant dyads is associated with differences in NAS severity in an independent cohort. Full‐term opioid‐exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next‐generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the ?18 (11.4% vs 4.4%, P = .0001), ?14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the ?169 (R = 0.43, P = .008), ?152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point‐wise with longer infant length of stay. Maternal associations remained significant point‐wise for ?169 (β = 0.07, P = .007) and on an experiment‐wise level for +84 (β = ?0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.     

TNF‐α‐induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini‐pigs

This experimental study was designed to clarify the relationship between cardiomyocyte apoptosis and tumour necrosis factor‐alpha (TNF‐α) expression, and confirm the effect of TNF‐α on cardiac dysfunction after coronary microembolization (CME) in mini‐pigs. Nineteen mini‐pigs were divided into three groups: sham‐operation group (n = 5), CME group (n = 7) and adalimumab pre‐treatment group (n = 7; TNF‐α antibody, 2 mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0‐T) was performed at baseline, 6th hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac‐TUNEL staining, and caspase‐3 and caspase‐8 were detected by RT‐PCR and immunohistochemistry. Furthermore, serum TNF‐α, IL‐6 and troponin T were analysed, while myocardial expressions of TNF‐α and IL‐6 were detected. Both TNF‐α expression (serum level and myocardial expression) and average number of apoptotic cardiomyocyte nuclei were significantly increased in CME group compared with the sham‐operation group. Six hours after CME, left ventricular end‐systolic volume (LVESV) was increased and the left ventricular ejection fraction (LVEF) was decreased in CME group. Pre‐treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 54.9 ± 2.3% versus 50.4 ± 3.9%, P = 0.036; 1 week: 56.7 ± 4.2% versus 52.7 ± 2.9%, P = 0.041), but also suppressed cardiomyocyte apoptosis and the expression of caspase‐3 and caspase‐8. Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely correlated with LVEF (r = ?0.535, P = 0.022). TNF‐α‐induced cardiomyocyte apoptosis is likely involved in cardiac dysfunction after CME. TNF‐α antibody therapy suppresses cardiomyocyte apoptosis and improves early cardiac function after CME.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake

Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70?±?12 years old), and BMI (12 normal-weight/12 obese; mean 28.1?±?6.7 kg/m²). Blood cell DNA was isolated and DNA methylation levels of TNF-α (?186 to +349 bp) and PON (?231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (?297 to ?185). Total TNF-α promoter methylation was lower in stroke patients (p?<?0.001) and showed no interaction with body composition (p?=?0.807). TNF-α and PON total methylation levels correlated each other (r?=?0.44; p?=?0.031), especially in stroke patients (r?=?0.72; p?=?0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p?=?0.027) and the region containing three CpGs (from ?170 to ?162 bp) to the percentage of lipid intake and dietary indexes (p?<?0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p?=?0.021), waist circumference (p?=?0.020), and energy intake (p?=?0.018), whereas +214 was associated to the quality of the diet (p?<?0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.     

Increased Expression of DNA Methyltransferase 3a in Obese Adipose Tissue: Studies With Transgenic Mice

Epigenetic mechanisms are likely to be involved in the development of obesity. This study was designed to examine the role of a DNA methyltransferase (Dnmt3a), in obese adipose tissue. The gene expression of Dnmts was examined by quantitative real‐time PCR analysis. Transgenic mice overexpressing Dnmt3a in the adipose tissue driven by the aP2 promoter were created (Dnmt3a mice). DNA methylation of downregulated genes was examined using bisulfite DNA methylation analysis. Dnmt3a mice were fed a methyl‐supplemented or high‐fat diet, and subjected to body weight measurement and gene expression analysis of the adipose tissue. Expression of Dnmt3a was markedly upregulated in the adipose tissue of obese mice. The complementary DNA (cDNA) microarray analysis of Dnmt3a mice revealed a slight decrease in the gene expression of secreted frizzled‐related protein 1 (SFRP1) and marked increase in that of interferon responsive factor 9 (IRF9). In the SFRP1 promoter, DNA methylation was not markedly increased in Dnmt3a mice relative to wild‐type mice. In experiments with a high‐fat diet or methyl‐supplemented diet, body weight did not differ significantly with the genotypes. Gene expression levels of inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1) were higher in Dnmt3a mice than in wild‐type mice on a high‐fat diet. This study suggests that increased expression of Dnmt3a in the adipose tissue may contribute to obesity‐related inflammation. The data highlight the potential role of Dnmt3a in the adult tissue as well as in the developing embryo and cancer.     

Fine‐scale population epigenetic structure in relation to gastrointestinal parasite load in red grouse (Lagopus lagopus scotica)

Epigenetic modification of cytosine methylation states can be elicited by environmental stresses and may be a key process affecting phenotypic plasticity and adaptation. Parasites are potent stressors with profound physiological and ecological effects on their host, but there is little understanding in how parasites may influence host methylation states. Here, we estimate epigenetic diversity and differentiation among 21 populations of red grouse (Lagopus lagopus scotica) in north‐east Scotland and test for association of gastrointestinal parasite load (caecal nematode Trichostrongylus tenuis) with hepatic genome‐wide and locus‐specific methylation states. Following methylation‐sensitive AFLP (MSAP), 129 bands, representing 73 methylation‐susceptible and 56 nonmethylated epiloci, were scored across 234 individuals. The populations differed significantly in genome‐wide methylation levels and were also significantly epigenetically (F_SC = 0.0227; P < 0.001) and genetically (F_SC = 0.0058; P < 0.001) differentiated. Parasite load was not associated with either genome‐wide methylation levels or epigenetic differentiation. Instead, we found eight disproportionately differentiated epilocus‐specific methylation states (F_ST outliers) using bayescan software and significant positive and negative association of 35 methylation states with parasite load from bespoke generalized estimating equations (GEE), simple logistic regression (sam ) and Bayesian environmental analysis (bayenv 2). Following Sanger sequencing, genome mapping and geneontology (go ) annotation, some of these epiloci were linked to genes involved in regulation of cell cycle, signalling, metabolism, immune system and notably rRNA methylation, histone acetylation and small RNAs. These findings demonstrate an epigenetic signature of parasite load in populations of a wild bird and suggest intriguing physiological effects of parasite‐associated cytosine methylation.     

Association of Pericardial Fat With Liver Fat and Insulin Sensitivity After Diet‐Induced Weight Loss in Overweight Women

Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity‐related insulin resistance. Because PAT is a well‐known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2–46.8 kg/m², 22–41 years) followed a 14.2 ± 4‐weeks low‐calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual‐energy X‐ray absorptiometry and intrahepatocellular lipids (IHCL) by (¹)H‐magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA_IR) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA_IR (r = 0.46), and M value (r = ?0.40; all P < 0.05). During intervention, body weight decreased by ?8.5%, accompanied by decreases of ?12% PAT, ?13% VAT, ?44% IHCL, ?10% HOMA2‐%B, and +24% as well as +15% increases in HOMA2‐%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = ?0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA_IR and HOMA2‐%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross‐sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.     

Association of the TNF‐α−308 G/A Promoter Polymorphism with Insulin Resistance in Obesity

Objective: Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)‐α is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (?308 G/A) of the TNF‐α gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population. Research Methods and Procedures: Obese, non‐diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction‐restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance. Results: The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high‐density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r = ?0.710; p < 0.001) occurred in subjects with the A allele only. Discussion: The ?308 G/A TNF‐α gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.     

Catechol‐O‐methyltransferase gene methylation and substance use in adolescents: the TRAILS study

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol‐O‐methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val^108/158Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val^108/158Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age = 16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self‐report questionnaires. From blood samples, COMT Val^108/158Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB‐COMT promoter methylation was associated with non‐daily smoking [odds ratio (OR) = 1.82, P = 0.03], but not with daily smoking (OR = 1.20, P = 0.34), MB‐COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB‐COMT promoter methylation were less likely to be high‐frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S‐COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Sex‐ and Depot‐Dependent Differences in Adipogenesis in Normal‐Weight Humans

To elucidate cellular mechanisms of sex‐related differences in fat distribution, we determined body fat distribution (dual‐energy X‐ray absorptiometry and single‐slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early‐differentiated adipocytes (aP2⁺CD68^?) in the stromovascular fraction (SVF) in the upper and lower body of normal‐weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18–49 years, BMI: 18–26 kg/m²). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor‐γ (PPARγ) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor‐α (TNFα)–induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper‐body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men.     

Predictors of Long‐term Weight Maintenance

Objective: The purpose of this study was to evaluate available variables of a long‐term weight maintenance study to investigate possible factors predisposing to weight regain after a period of weight loss. Research Methods and Procedures: The Maastricht Weight Maintenance Study is an ongoing longitudinal study of healthy men and women (29 men and 62 women; 18 to 65 years of age; BMI = 30.2 ± 3.1 kg/m²). A variety of parameters were measured before and after a very‐low‐energy diet and after a follow‐up of at least 2 years. Results: Mean weight loss was 7.9 ± 3.6 kg, and percent weight regain was 113.8 ± 98.1%. Percent BMI regain was negatively associated with an increase in dietary restraint (r = ?0.47, p < 0.05). Percent weight regain was negatively correlated with baseline resting metabolic rate (r = ?0.38, p = 0.01) and baseline fat mass (r = ?0.24, p = 0.05) and positively correlated with the magnitude of change in body weight (BW) expressed as maximum amplitude of BW (r = 0.21, p < 0.05). In addition, amplitude of BW was positively correlated with the frequency of dieting (r = 0.57, p < 0.01). Discussion: The best predictors for weight maintenance after weight loss were an increase in dietary restraint during weight loss, a high baseline resting metabolic rate, a relatively high baseline fat mass favoring a fat‐free mass–sparing effect during weight loss, a rather stable BW, and a low frequency of dieting. Therefore, BW maintenance after BW loss seems to be a multifactorial issue, including mechanisms that regulate an individuals’ energy expenditure, body composition, and eating behavior in such a way that energy homeostasis is maintained.     

25‐Hydroxyvitamin D Concentration Correlates With Insulin‐Sensitivity and BMI in Obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25‐hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin‐sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin‐sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin‐sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50 nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low‐density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin‐sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = ?0.58; P = 0.01), PTH (r = ?0.44; P < 0.01), insulin‐sensitivity (r = 0.43; P < 0.01), total (r = ?0.34; P = 0.030) and LDL (r = ?0.40; P = 0.023) (but not high‐density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin‐sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = ?0.52; P < 0.01), whereas insulin‐sensitivity was not significant. Our study suggested that there is no cause–effect relationship between vitamin D and insulin‐sensitivity. In obesity, both low 25(OH)D concentration and insulin‐resistance appear to be dependent on the increased body size.