Intermittent fasting modulates human gut microbiota diversity in a phenotype-dependent manner: a systematic review.

Cumulative evidence suggests that intermittent fasting (IF) has beneficial effects on human metabolic health. It has been indicated that its impact on the gut microbiota may mediate these beneficial effects. As a result, we hypothesized that IF may impact the human gut microbiota. A systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol using the PubMed, Scopus, and CINAHL databases. We registered our systematic review protocol in PROSPERO under registration number CRD42021270050. Human intervention studies published until April 30, 2023, were included. The quality of the included studies was assessed using National Institutes of Health (NIH) quality assessment study tools for intervention studies. The search in the database returned 166 studies, of which 13 matched all criteria for the final qualitative analysis. The body of evidence suggests that IF modulates human gut microbiota alpha and beta diversity in lean (relatively healthy) and relatively healthy overweight/obese individuals but not in individuals with metabolic syndrome. Furthermore, IF also alters human gut microbiota composition in all phenotypes. Of interest, the gut microbiota taxa or microbial metabolites after an IF intervention are associated with metabolic markers. According to this review, IF influences the diversity and taxonomic levels of the human gut microbiota. Individual metabolic phenotypes may alter the effect of IF on the diversity and taxonomic levels of the gut microbiota.

Novel Functional Food Properties of Forest Onion (Eleutherine bulbosa Merr.) Phytochemicals for Treating Metabolic Syndrome: New Insights from a Combined Computational and In Vitro Approach.

Metabolic syndrome is a global health problem. The use of functional foods as dietary components has been increasing. One food of interest is forest onion extract (FOE). This study aimed to investigate the effect of FOE on lipid and glucose metabolism in silico and in vitro using the 3T3-L1 mouse cell line. This was a comprehensive study that used a multi-modal computational network pharmacology analysis and molecular docking in silico and 3T3-L1 mouse cells in vitro. The phytochemical components of FOE were analyzed using untargeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Next, an in silico analysis was performed to determine FOE's bioactive compounds, and a toxicity analysis, protein target identification, network pharmacology, and molecular docking were carried out. FOE's effect on pancreatic lipase, α-glucosidase, and α-amylase inhibition was determined. Finally, we determined its effect on lipid accumulation and MAPK8, PPARG, HMGCR, CPT-1, and GLP1 expression in the preadipocyte 3T3-L1 mouse cell line. We showed that the potential metabolites targeted glucose and lipid metabolism in silico and that FOE inhibited pancreatic lipase levels, α-glucosidase, and α-amylase in vitro. Furthermore, FOE significantly (p < 0.05) inhibits targeted protein expressions of MAPK8, PPARG, HMGCR, CPT-1, and GLP-1 in vitro in 3T3-L1 mouse cells in a dose-dependent manner. FOE contains several metabolites that reduce pancreatic lipase levels, α-glucosidase, α-amylase, and targeted proteins associated with lipid and glucose metabolism in vitro.

The Effects of Hepatogomax Enteral Formula on Systemic Inflammation, Caecum Short-Chain Fatty Acid Levels, and Liver Histopathology in Thioacetamide-Induced Rats.

Liver damage characterized by fibrosis and necrosis can worsen the condition of liver disease. Liver disease is associated with impaired immune response and may affect short-chain fatty acid (SCFA) gut metabolites. Hepatogomax enteral formula was developed, which contains brain-chain amino acids (BCAAs) and middle-chain triglycerides (MCTs), which could repair liver tissue damage, improve the inflammatory status, and modulate SCFA in liver damage. The study aimed to determine the effect of hepatogomax on liver tissue repair, inflammation (TNF-α and IL-6), and SCFA levels in thioacetamide (TAA)-induced rats. The induction of TAA causes liver steatosis, increasing TNF-α and IL-6, and decreasing SCFA levels. Hepatogomax at a dose of 14.6 g/200 gBW significantly reduces TNF-α and IL-6 levels and increases SCFA levels (p < 0.05). The number of steatosis between groups P2 and P3 was lower as compared to a group of negative control [K2] (p < 0.05). Hepatogomax, in a dose-dependent manner, may repair liver tissue and improve inflammatory response and SCFA levels in TAA-induced rats.

The Association between Unhealthy Food Consumption and Impaired Glucose Metabolism among Adults with Overweight or Obesity: A Cross-Sectional Analysis of the Indonesian Population.

Background: It has been shown that dietary patterns are associated with glucose control. However, the association between the types of food consumed and blood glucose in overweight or obese individuals is still unclear. The present study aimed to determine the association between unhealthy food consumption and impaired glucose metabolism in adults with overweight or obesity. Methods: The analysis presented in this study was based on the data from a population-based, cross-sectional, nationally representative survey (Indonesian Basic Health Research 2018/RISKESDAS 2018). The body mass index (BMI) was calculated as weight (kg)/height squared (m2) and was determined based on the World Health Organization (WHO) criteria for the Asian population. A validated questionnaire and food card were used to assess the diet. Fasting plasma glucose and 2-hpost-prandial glucose were employed to determine blood glucose markers. Results: In total, 8752 adults with overweight or obesity were included in this analysis. We found that consumption of sweet, grilled, and processed foods was associated with impaired fasting plasma glucose (IFG) before and after adjustment (p < 0.05). Consumption of high-fat foods was also associated with impaired glucose tolerance (IGT) for all models tested (p < 0.05). Furthermore, all models showed a link between processed food consumption and combined glucose intolerance (CGI) (p ≤ 0.001). Conclusions: Differential food group consumption was associated with IFG, IGT, and CGI in Indonesian adults who were overweight or obese.

Dietary Supplementation of Caulerpa racemosa Ameliorates Cardiometabolic Syndrome via Regulation of PRMT-1/DDAH/ADMA Pathway and Gut Microbiome in Mice.

This study evaluated the effects of an aqueous extract of Caulerpa racemosa (AEC) on cardiometabolic syndrome markers, and the modulation of the gut microbiome in mice administered a cholesterol- and fat-enriched diet (CFED). Four groups of mice received different treatments: normal diet, CFED, and CFED added with AEC extract at 65 and 130 mg/kg body weight (BW). The effective concentration (EC50) values of AEC for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and lipase inhibition were lower than those of the controls in vitro. In the mice model, the administration of high-dose AEC showed improved lipid and blood glucose profiles and a reduction in endothelial dysfunction markers (PRMT-1 and ADMA). Furthermore, a correlation between specific gut microbiomes and biomarkers associated with cardiometabolic diseases was also observed. In vitro studies highlighted the antioxidant properties of AEC, while in vivo data demonstrated that AEC plays a role in the management of cardiometabolic syndrome via regulation of oxidative stress, inflammation, endothelial function (PRMT-1/DDAH/ADMA pathway), and gut microbiota.

Mangrove fruit (Bruguiera gymnorhiza) increases circulating GLP-1 and PYY, modulates lipid profiles, and reduces systemic inflammation by improving SCFA levels in obese wistar rats.

Bruguiera gymnorhiza (BG) has potential as a functional food because of its dietary fibre content and bioactive components such as flavonoids and phenolic compounds. However, it is not studied in the context of diet-related disease prevention. In the present study, we aimed to investigate the effects of Bruguiera gymnorhiza fruit flour (BGF) on satiety hormone, lipid profile, systemic inflammation, body weight, and caecum SCFA levels in diet-induced obese rats. A total of 28 obese male Wistar rats were divided into four groups. Group 1 (K1) was given a standard chow, group 2 (K2) standard chow + orlistat, group 3 (P1) standard chow + BGF 2 g/200 g BW/day, and group 4 (P2) standard chow + BGF 4 g/200 g BW/day for 28 days. The levels of GLP-1, PYY, total cholesterol (TC), triglyceride (TG), HDL, IL-6, TNF-α, and body weight were measured before and after the intervention; meanwhile, the caecum SCFA levels were assessed only after the intervention. In this study, BGF intervention increased the dose-dependent plasma GLP-1 and PYY levels (P < 0.000). In addition, BGF intervention also decreased lipid profiles (TC & TG) (P < 0.000, respectively) and systemic inflammation in a dose-dependent manner. Finally, acetate, propionate, and total SCFA concentrations were higher in the BGF intervention group (P2) compared to the other groups (p < 0.05). The SCFA levels were associated with satiety hormones, lipids, and systemic inflammation (P < 0.05). The BGF intervention improved satiety hormone, lipid profile, systemic inflammation, and SCFA levels.

Amelioration of obesity-related metabolic disorders via supplementation of Caulerpa lentillifera in rats fed with a high-fat and high-cholesterol diet.

Dietary modification, including functional foods, could reduce comorbidities due to obesity. An increase in serum glucose and lipids is often seen in obesity. Furthermore, obesity is also characterized by a decrease in antioxidant capacity (i.e., decrease in superoxide dismutase/SOD) and downregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). It has been well established that PGC-1α is important to regulate mitochondrial biogenesis. Sea grapes (Caulerpa lentillifera) are known as a traditional food in many Asia-Pacific countries. Recent evidence suggests that sea grapes have many beneficial properties as functional foods and may have potential therapeutic functions. We investigated the effect of sea grapes (C. lentillifera) on serum glucose, lipids, PGC-1α, and protein levels of SOD in the liver of Rattus norvegicus, which is induced with a high-fat and high-cholesterol diet. A total of four groups were made, each containing ten male Rattus norvegicus; group A received a standard dry pellet diet as control, group B received cholesterol- and fat-enriched diets (CFED), groups C and D received CFED and 150 and 450 mg/kg body weight (BW) of sea grape extract, respectively, for 4 weeks. Serum glucose and cholesterol were assessed using a blood auto-analyzer. Serum PGC-1α was measured using ELISA. SOD levels were calculated using the superoxide dismutase assay kit by Sigma-Aldrich with blood taken from liver tissue. In this study, sea grape extracts improved total cholesterol levels better than the CFED and normal groups. The efficacy of total cholesterol improvement was similar between the two doses of sea grape extract. Furthermore, sea grape extract increased PCG-1α levels, especially with the dose of 150 mg/kg BW. Blood glucose was also lower in the groups of sea grape extract. Interestingly, the groups treated with sea grapes extract exhibited higher levels of liver SOD compared to the normal and CFED groups. To conclude, sea grapes (C. lentillifera) have promising potential for anti-hyperglycemia and anti-hypercholesterolemia, and for reducing oxidative stress, and providing various health benefits for metabolic disorders.

Exercise training in the management of overweight and obesity in adults: Synthesis of the evidence and recommendations from the European Association for the Study of Obesity Physical Activity Working Group.

There is a need for updated practice recommendations on exercise in the management of overweight and obesity in adults. We summarize the evidence provided by a series of seven systematic literature reviews performed by a group of experts from across Europe. The following recommendations with highest strength (Grade A) were derived. For loss in body weight, total fat, visceral fat, intra-hepatic fat, and for improvement in blood pressure, an exercise training program based on aerobic exercise at moderate intensity is preferentially advised. Expected weight loss is however on average not more than 2 to 3 kg. For preservation of lean mass during weight loss, an exercise training program based on resistance training at moderate-to-high intensity is advised. For improvement in insulin sensitivity and for increasing cardiorespiratory fitness, any type of exercise training (aerobic, resistance, and combined aerobic or resistance) or high-intensity interval training (after thorough assessment of cardiovascular risk and under supervision) can be advised. For increasing muscular fitness, an exercise training program based preferentially on resistance training alone or combined with aerobic training is advised. Other recommendations deal with the beneficial effects of exercise training programs on energy intake and appetite control, bariatric surgery outcomes, and quality of life and psychological outcomes in management of overweight and obesity.

Effect of exercise training before and after bariatric surgery: A systematic review and meta-analysis.

We aimed to assess the effectiveness of exercise training programs in adults with severe obesity undergoing bariatric surgery. A systematic search of controlled trials published up to October 2019 that assigned participants to either a preoperative or postoperative exercise training group or a nonexercise group was performed. Meta-analyses were conducted using random-effects models. Twenty-two training programs were assessed (18 performed after bariatric surgery). The effect of preoperative exercise training on postsurgery outcomes was reported in only one study. Compared with the control condition without exercise, postoperative exercise training led to higher weight loss (N = 14, mean difference [95% CI] = -1.8 [-3.2; -0.4] kg, P = 0.01), fat loss (N = 9, P = 0.01), increase in VO2 max (N = 8, P < 0.0001), and increase in muscle strength (N = 9, P < 0.0001). No significant effect was found on lean body mass (N = 11). Preliminary evidence suggests a beneficial effect of postoperative exercise training on bone mineral density (N = 3, P < 0.001) and weight maintenance after the end of the intervention (N = 2, P < 0.001) but no significant effect on quality of life (N = 2), habitual physical activity (N = 2), or cardiometabolic outcomes (N < 4). In conclusion, exercise training performed after bariatric surgery improves physical fitness and leads to a small additional weight and fat loss and may prevent bone loss and weight regain after bariatric surgery.

Effect of exercise on cardiometabolic health of adults with overweight or obesity: Focus on blood pressure, insulin resistance, and intrahepatic fat-A systematic review and meta-analysis.

This systematic review examined the impact of exercise intervention programs on selected cardiometabolic health indicators in adults with overweight or obesity. Three electronic databases were explored for randomized controlled trials (RCTs) that included adults with overweight or obesity and provided exercise-training interventions. Effects on blood pressure, insulin resistance (homeostasis model of insulin resistance, HOMA-IR), and magnetic resonance measures of intrahepatic fat in exercise versus control groups were analyzed using random effects meta-analyses. Fifty-four articles matched inclusion criteria. Exercise training reduced systolic and diastolic blood pressure (mean difference, MD = -2.95 mmHg [95% CI -4.22, -1.68], p < 0.00001, I2  = 63% and MD = -1.93 mmHg [95% CI -2.73, -1.13], p < 0.00001, I2  = 54%, 60 and 58 study arms, respectively). Systolic and diastolic blood pressure decreased also when considering only subjects with hypertension. Exercise training significantly decreased HOMA-IR (standardized mean difference, SMD = -0.34 [-0.49, -0.18], p < 0.0001, I2 = 48%, 37 study arms), with higher effect size in subgroup of patients with type 2 diabetes (SMD = -0.50 [95% CI: -0.83, -0.17], p = 0.003, I2 = 39%). Intrahepatic fat decreased significantly after exercise interventions (SMD = -0.59 [95% CI: -0.78, -0.41], p < 0.00001, I2  = 0%), with a larger effect size after high-intensity interval training. In conclusion, exercise training is effective in improving cardiometabolic health in adults with overweight or obesity also when living with comorbitidies.

Effect of exercise training interventions on energy intake and appetite control in adults with overweight or obesity: A systematic review and meta-analysis.

This systematic review examined the impact of exercise training interventions on energy intake (EI) and appetite control in adults with overweight/obesity (≥18 years including older adults). Articles were searched up to October 2019. Changes in EI, fasting appetite sensations, and eating behavior traits were examined with random effects meta-analysis, and other outcomes were synthesized qualitatively. Forty-eight articles were included (median [range] BMI = 30.6 [27.0-38.4] kg/m2 ). Study quality was rated as poor, fair, and good in 39, seven, and two studies, respectively. Daily EI was assessed objectively (N = 4), by self-report (N = 22), with a combination of the two (N = 4) or calculated from doubly labeled water (N = 1). In studies rated fair/good, no significant changes in pre-post daily EI were found and a small but negligible (SMD < 0.20) postintervention difference when compared with no-exercise control groups was observed (five study arms; MD = 102 [1, 203] kcal). There were negligible-to-small pre-post increases in fasting hunger and dietary restraint, decrease in disinhibition, and some positive changes in satiety and food reward/preferences. Within the limitations imposed by the quality of the included studies, exercise training (median duration of 12 weeks) leads to a small increase in fasting hunger and a small change in average EI only in studies rated fair/good. Exercise training may also reduce the susceptibility to overconsumption (PROSPERO: CRD42019157823).

Effective behavior change techniques to promote physical activity in adults with overweight or obesity: A systematic review and meta-analysis.

Multicomponent behavior change interventions are typically used in weight management, but results are largely heterogeneous and modest. Determining which techniques (behavior change technique [BCTs]) are more effective in changing behavior is thus required. This study aimed to identify the most effective BCTs for increasing physical activity (PA) in digital and face-to-face behavior change interventions in adults with overweight/obesity. Four databases were searched for eligible studies until October 2019. BCTs were coded using BCTTv1 and MBCT taxonomies. Sixty-two RCTs were included. Meta-regressions were performed to explore BCTs' moderating role. Five BCTs showed significant moderator effects on PA in digital interventions: goal setting behavior, goal setting outcome, graded tasks, social incentive, and self-monitoring of behavior (adjusted R2 's = 0.15-0.51). One BCT showed significant moderator effects on PA in face-to-face interventions, behavioral practice and rehearsal (adjusted R2 = 0.22). Multivariate and sensitivity analysis generally led to similar findings. Effective BCTs for increasing PA in adults with overweight/obesity in digital and face-to-face interventions seem to differ. Evidence suggests that using goal setting, social incentive, and graded tasks might help improve PA in digital interventions while avoiding inconsistent self-monitoring of behavior. In face-to-face interventions, prompting behavioral practice and rehearsal might lead to better PA outcomes. Still, further studies are needed. Implications of the current findings are discussed.

Effect of exercise training on weight loss, body composition changes, and weight maintenance in adults with overweight or obesity: An overview of 12 systematic reviews and 149 studies.

This overview of reviews aimed to summarize the effects of exercise training programs on weight loss, changes in body composition, and weight maintenance in adults with overweight or obesity. A systematic search of systematic reviews and meta-analyses (SR-MAs) published between 2010 and December 2019 was performed. Only SR-MAs of controlled trials were included. The mean difference (MD) or standardized MD (SMD) were extracted from SR-MAs. Twelve SR-MAs (149 studies) were included. Exercise led to a significant weight loss (4 SR-MAs, MDs ranging from -1.5 to -3.5 kg), fat loss (4 SR-MAs, MDs ranging from -1.3 to -2.6 kg) and visceral fat loss (3 SR-MAs, SMDs ranging from -0.33 to -0.56). No difference in weight, fat, and visceral loss was found between aerobic and high-intensity interval training as long as energy expenditure was equal. Resistance training reduced lean mass loss during weight loss (1 SR-MA, MD: 0.8 [95%CI: 0.4-1.3] kg). No significant effect of exercise was found on weight maintenance (1 SR-MA). These findings show favorable effects of exercise training on weight loss and body composition changes in adults with overweight or obesity. Visceral fat loss may lead to benefits for cardiometabolic health. More research is needed to identify training modalities that promote weight maintenance.

Effect of different types of regular exercise on physical fitness in adults with overweight or obesity: Systematic review and meta-analyses.

This systematic review examined the effect of exercise training interventions on physical fitness in adults with overweight or obesity and compared the effectiveness of different types of exercise training. Four electronic databases were searched. Articles were included if they described randomized controlled trials of exercise training interventions and their effect on maximal oxygen consumption or muscle strength in adults with overweight or obesity. Changes in outcome parameters were analyzed using random effects meta-analyses for different training types (aerobic, resistance, combined aerobic plus resistance, and high-intensity interval training). Eighty-eight articles satisfied the inclusion criteria of which 66 (3964 participants) could be included in the meta-analyses. All training types increased VO2max (mean difference 3.82 ml/min/kg (95% CI 3.17, 4.48), P < 0.00001; I2 = 48%). In direct comparisons, resistance training was less effective in improving VO2max than aerobic training, HIIT was slightly more effective than aerobic training, and no difference between aerobic and combined aerobic plus resistance training was found. For muscle strength benefits, incorporation of resistance exercise in the training program is indicated. Exercise training increases VO2max and muscle strength in adults with overweight or obesity. Differences between training types should be weighed with other needs and preferences when health professionals advise on exercise training to improve physical fitness.

The safety and efficacy of supervised exercise on pregnant women with overweight/obesity: A systematic review and meta-analysis of randomized controlled trials.

Behavioural modification through physical activity and dietary counselling has been shown to have beneficial effects on pregnant women with overweight/obesity. Whether exercise alone with supervision (ie, supervised exercise) may also benefit for pregnant women with overweight/obesity is still unknown. This systematic review and meta-analysis aimed to determine the safety and efficacy of supervised exercise on pregnant women with overweight/obesity. PubMed, Cochrane library, Embase (Ovid), CINAHL (EBSCO), and Web of Science were used to search publications using a combination of main keywords "obesity", "exercise", "pregnant women", and "randomised controlled trial". From a total of 740 publications, 11 randomized controlled trials were included. All studies reported no adverse effects of supervised exercise on pregnant women with overweight/obesity. Of interest, this meta-analysis showed gestational weight gain (GWG) was lower in the supervised exercise group as compared to control (Mean difference 0.88 kg, 95%CI -1.73 to -0.03, P = .04). There was a significant effect of supervised exercise on post-prandial blood glucose (MD: -0.24, 95%CI -0.47 to -0.01, P = .04) and insulin resistance (HOMA-IR) (MD: -0.18, 95%CI -0.30 to -0.05, P = .005). There were no differences in risk of gestational diabetes mellitus, pre-eclampsia/gestational hypertension, and newborn outcomes (eg, infants birth weight, preterm birth incident, and gestational age) (all P > .05). This meta-analysis might suggest beneficial effects of supervised exercise on pregnant women with overweight/obesity to prevent excessive GWG, attenuates insulin resistance, and the post-prandial blood glucose level.

The Effect of Vitamin D Supplementation on Insulin Sensitivity: A Systematic Review and Meta-analysis.

BACKGROUND: Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE: This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION: PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION: The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS: Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n = 612) with placebo (n = 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference -0.01, 95% CI -0.12, 0.10; P = 0.87, I 2 = 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS: The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS: This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.

Vitamin D release across abdominal adipose tissue in lean and obese men: The effect of ß-adrenergic stimulation.

Obesity is characterized by a blunted lipolytic response in abdominal subcutaneous adipose tissue (SAT) and low circulating vitamin D levels. Here we investigated whether an impaired SAT lipolytic response coincides with an impaired SAT vitamin D release in eight lean and six obese men. 25-hydroxyvitamin D3 [25(OH)D3 ] and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] fluxes across SAT were measured using arterio-venous blood sampling in combination with AT blood flow measurements after an overnight fast and during 1-hr intravenous infusion of the non-selective ß-adrenergic agonist isoprenaline (20 ng·kg FFM-1 ·min-1 ). 1,25(OH)2 D3 was released across abdominal SAT during isoprenaline infusion in lean [-0.01 (-0.04 to 0.00) pmol*100 g tissue-1 *min-1 , p = .017 vs. zero flux], but not in obese men [0.01 (0.00 to 0.02) pmol*100 g tissue-1 *min-1 , p = .116 vs. zero flux], and accompanied by an impaired isoprenaline-induced lipolytic response in abdominal SAT of obese versus lean men. Isoprenaline had no significant effects on net 25(OH)D3 release across abdominal SAT and plasma vitamin D metabolites in lean and obese men. To conclude, a blunted isoprenaline-mediated lipolysis is accompanied by reduced release of 1,25(OH)2 D3 vitamin D across abdominal SAT in obesity.

Vitamin D deficiency in the aetiology of obesity-related insulin resistance.

The obese insulin-resistant state is often associated with low circulating concentration of vitamin D 25-hydroxyvitamin D3 [25(OH)D3 ]. Fat sequestration of vitamin D in the expanded obese adipose tissue mass has been pointed out as a plausible explanation for this circulating vitamin D deficiency. However, the putative mechanisms behind this hypovitaminosis D remain to be elucidated. The presence of vitamin D receptor and vitamin D-metabolizing enzymes in insulin-sensitive organs suggests that vitamin D may be involved in glucose and lipid metabolism and may be related to insulin sensitivity. Indeed, mainly in vitro studies support a role of vitamin D in regulating glucose and lipid metabolism in several insulin-sensitive tissues including adipose tissue, skeletal muscle, liver, as well as pancreatic insulin secretion. A potential role of vitamin D in gut barrier function and metabolism has also been suggested. This review summarizes recent knowledge on vitamin D deficiency in the aetiology of obesity-related insulin resistance and discusses potential underlying mechanisms. Finally, the role of vitamin D supplementation on insulin sensitivity and glycaemic control is discussed.

Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity.

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D3 [25(OH)D3] as well as plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity. Objective: To investigate the association between body mass index (BMI) and plasma 25(OH)D3 and 1,25(OH)2D3, AT VDR; between plasma 25(OH)D3, 1,25(OH)2D3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity. Design and Patients: This analysis included 92 adult individuals (BMI, >25 kg/m2). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H2]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR. Setting: University medical center. Main Outcome Measures: Plasma 25(OH)D3, 1,25(OH)2D3, 1,25(OH)2D3/25(OH)D3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity. Results: BMI was inversely associated with plasma 25(OH)D3 (ß = -0.274; P = 0.011) but not with plasma 1,25(OH)2D3. Plasma 25(OH)D3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)2D3 and 25(OH)D3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (ß = -0.207; P = 0.025). Conclusions: BMI was inversely associated with 25(OH)D3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity.

Effect of tuberculosis treatment on leptin levels, weight gain, and percentage body fat in Indonesian children.

PURPOSE: Tuberculosis (TB) remains a problem in the community. TB patients usually experience malnutrition, which is characterized by both decreased body weight (BW) and body fat percentage (BFP). Leptin, an important regulator of BW, also plays an important role in cellular immunity, which is integral to defense against Mycobacterium tuberculosis infection. We analyzed the effect of an anti-TB treatment regimen on the leptin level, BW, and BFP of children with TB. METHODS: The design of this study was a group interrupted time series. The subjects were children with probable TB according to clinical criteria based on an Indonesian scoring system adopted from the Consensus of Expert Panel. BW; BFP; energy intake; fat and protein intake; and leptin levels before, 2 months after (intensive phase), and 6 months after (continuation phase) anti-TB treatment, were measured. About 40 children, aged 5-14 years, participated in this study. RESULTS: The BW, BFP and leptin level increased from before treatment to after completion of the intensive phase and still showed an increased during the continuation phase: BW 18.65 kg, 19.75 kg, and 20.85 kg; BFP 18.3%, 19.5%, and 20.2%; and leptin level 1.9 mg/dL, 3.07 mg/dL, and 3.4 mg/dL, respectively (P<0.01). CONCLUSION: Leptin level, BW, and BFP increased throughout the course of anti-TB treatment, compared with pretreatment values. Further research is needed to compare the results with data for healthy children.