Epigoitrin alleviates lipid and glucose metabolic disorders induced by a high-fat diet.

As living standards improve, obesity has become an increasingly serious health problem. Natural extracts from a wide range of sources are non-toxic and have significant potential as drugs for the prevention and treatment of obesity. We assessed 243 natural small molecules in a HepG2 fat accumulation model and found that epigoitrin (EP) from Radix isatidis reduced intracellular fat deposition, increased short-chain acyl CoA dehydrogenase (SCAD) activity, promoted glucose uptake and glycogen storage, increased ATP production and reduced glutathione (GSH) content, reduced reactive oxygen species (ROS), and enhanced superoxide dismutase (SOD) activity. In a murine high-fat diet model, the addition of EP to the high-fat diet significantly reduced fat deposition, increased glucose tolerance, improved insulin sensitivity, and increased energy expenditure. In conclusion, EP alleviated obesity caused by a high-fat diet and improved disorders of lipid and glucose metabolism.

Chronic binge alcohol and ovariectomy-mediated impaired insulin responsiveness in SIV-infected female rhesus macaques.

Aging people living with HIV (PLWH), especially postmenopausal women may be at higher risk of comorbidities associated with HIV, antiretroviral therapy (ART), hypogonadism, and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-ß in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX) on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Female macaques were administered CBA (12-15 g/kg/wk) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIVmac251, and initiated on antiretroviral therapy (ART) 2.5 mo postinfection. After 1 mo of ART, macaques were randomized to OVX or sham surgeries (n = 7 or 8/group), and euthanized 8 mo post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected time points. Pancreatic gene expression and islet morphology were determined at study endpoint. There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG (P = 0.06). CBA and OVX decreased the expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction that may be exacerbated by alcohol use and ovarian hormone loss.

Oxidized Pork Induces Disorders of Glucose Metabolism in Mice.

SCOPE: Consumption of red meat, particularly processed red meat, has been reported to be associated with type 2 diabetes risk, and oxidized proteins and amino acids may be involved in this process. This study explores the effects of pork with varying degrees of oxidative injury caused by cooking on glucose metabolism in mice. METHODS AND RESULTS: Cooked pork is freeze-dried to prepare animal feed. Mice are fed either a control diet (CON), a low- (LOP), or a high-oxidative injury pork diet (HOP) for 12 weeks. Intake of HOP causes hyperglycemia, hypoinsulinemia, and impaired glucose tolerance, indicating a glucose metabolism disorder. Accumulation of oxidation products increases oxidative stress and inflammatory response, which impairs pancreatic islet ß cells function and reduces insulin secretion. Moreover, HOP-mediated hyperglycemia can be partly attributed to elevated hepatic glucose output, as indicated by increased gluconeogenesis and glycogenolysis, and decreased glycolysis and glycogen content. Changes in these processes may be regulated by reduced insulin levels and suppression of the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and its downstream signaling molecules. CONCLUSION: HOP intake induces disorders of glucose metabolism by impairing pancreatic insulin secretion and increasing hepatic glucose output. Protein oxidation plays a key role in abnormal glucose metabolism induced by HOP.

Thioredoxin deficiency exacerbates vascular dysfunction during diet-induced obesity in small mesenteric artery in mice.

OBJECTIVE: Thioredoxin (Trx) is a small cellular redox protein with established antioxidant and disulfide reductase properties. We hypothesized that Trx deficiency in mice would cause increased oxidative stress with consequent redox imbalance that would exacerbate obesity-induced vascular dysfunction. METHODS: Non-transgenic (NT, C57BL/6) and dominant-negative Trx (dnTrx-Tg, low levels of redox-active protein) mice were either fed a normal diet (NC) or high fat diet plus sucrose (HFS) diet for 4 months (3-month HFD+ 1-month HFS). Weight gain, glucose tolerance test (GTT), insulin tolerance test (ITT), and other metabolic parameters were performed following NC or HFS diet. Arterial structural remodeling and functional parameters were assessed by myography. RESULTS: Our study found that dnTrx mice with lower levels of active Trx exacerbated myogenic tone, inward arterial remodeling, arterial stiffening, phenylephrine-induced contraction, and endothelial dysfunction of MA. Additionally, FeTMPyP, a peroxynitrite decomposition catalyst, acutely decreased myogenic tone and contraction and normalized endothelial function in MA from dnTrx-Tg mice on HFS via increasing nitric oxide (NO)-mediated relaxation. CONCLUSIONS: Our results indicate that deficiency of active Trx exacerbates MA contractile and relaxing properties during diet-induced obesity demonstrating that loss of redox balance in obesity is a key mechanism of vascular endothelial dysfunction.

Sodium butyrate arrests pancreato-hepatic synchronous uric acid and lipid dysmetabolism in high fat diet fed Wistar rats.

High fat diet (HFD) is a risk factor for metabolic syndrome which is characterized by overt glucose dysmetabolism and tissue derangement. The liver and pancreas are important metabolic tissues with anatomical proximity sharing splanchnic and mesenteric circulation but it is unclear whether, there is an associated metabolic status between the two organs in health and disease. Uric acid (UA) hypersecretion and ectopic lipid accumulation are characteristic pathophysiology of an array of non-communicable diseases. Sodium butyrate (BUT) is reputed for therapeutic roles in metabolic derangement. Therefore, the present study investigated synchrony in hepatic and pancreatic UA and lipid metabolic status in HFD-induced glucose dysregulation and probed the beneficial effects of BUT. Twenty-four female Wistar rats were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high fat diet and distilled water (po) or high fat diet and sodium butyrate. Results showed that HFD increased plasma, pancreatic and hepatic triglyceride, triglyceride-glucose index, malondialdehyde, uric acid (UA), lactate dehydrogenase but reduced glucose-6-phosphate dehydrogenase. Histological analysis revealed hepatic and pancreatic architectural derangement and cellular degeneration in HFD-fed animals. However, BUT reversed the HFD-induced systemic, pancreatic and hepatic synchronous dysmetabolism with evidence of improved histology. HFD-induced lipid and UA alterations were synchronous in the pancreas and liver. BUT elicits beneficial effects on systemic and tissue HFD-induced deleterious metabolic changes which were synchronized in pancreas and liver of rats.

Consumption of Foods Derived from Subsidized Crops Remains Associated with Cardiometabolic Risk: An Update on the Evidence Using the National Health and Nutrition Examination Survey 2009-2014.

In this study, we examined the associations between the consumption of foods derived from crops subsidized under the 2008 United States (US) Farm Bill and cardiometabolic risk factors and whether the magnitude of these associations has changed since the 2002 US Farm Bill. Four federal databases were used to estimate daily consumption of the top seven subsidized commodities (corn, soybeans, wheat, rice, sorghum, dairy, and livestock) and to calculate a subsidy score (0-1 scale) for Americans' daily dietary intake during 2009-2014, with a higher score indicative of a higher proportion of the diet derived from subsidized commodities. The cardiometabolic risk factors included obesity, abdominal adiposity, hypertension, dyslipidemia, and dysglycemia. Linear and logistic regression models were adjusted for age, sex, race/ethnicity, the poverty-income ratio, the smoking status, educational attainment, physical activity, and daily calorie intake. During 2009-2014, adults with the highest subsidy score had higher probabilities of obesity, abdominal adiposity, and dysglycemia compared to the lowest subsidy score. After the 2002 Farm Bill (measured using data from 2001-2006), the subsidy score decreased from 56% to 50% and associations between consuming a highly-subsidized diet and dysglycemia did not change (p = 0.54), whereas associations with obesity (p = 0.004) and abdominal adiposity (p = 0.002) significantly attenuated by more than half. The proportion of calories derived from subsidized food commodities continues to be associated with adverse cardiometabolic risk factors, though the relationship with obesity and abdominal adiposity has weakened in recent years.

Zinc Supplementation Alleviates Lipid and Glucose Metabolic Disorders Induced by a High-Fat Diet.

Zinc deficiency is a risk factor for the development of obesity and diabetes. Studies have shown lower serum zinc levels in obese individuals and those with diabetes. We speculate that zinc supplementation can alleviate obesity and diabetes and, to some extent, their complications. To test our hypothesis, we investigated the effects of zinc supplementation on mice with high-fat diet (HFD)-induced hepatic steatosis in vivo and in vitro by adding zinc to the diet of mice and the medium of HepG2 cells. Both results showed that high levels of zinc could alleviate the glucose and lipid metabolic disorders induced by a HFD. High zinc can reduce glucose production, promote glucose absorption, reduce lipid deposition, improve HFD-induced liver injury, and regulate energy metabolism. This study provides novel insight into the treatment of non-alcoholic fatty liver disease and glucose metabolic disorder.

Update on Diabetes Mellitus and Glucose Metabolism Alterations in Prader-Willi Syndrome.

PURPOSE OF REVIEW: This review summarizes our current knowledge on type 2 diabetes mellitus (T2DM) and glucose metabolism alterations in Prader-Willi syndrome (PWS), the most common syndromic cause of obesity, and serves as a guide for future research and current best practice. RECENT FINDINGS: Diabetes occurs in 10-25% of PWS patients, usually in adulthood. Severe obesity is a significant risk factor for developing of T2DM in PWS. Paradoxically, despite severe obesity, a relative hypoinsulinemia, without the expected insulin resistance, is frequently observed in PWS. The majority of PWS subjects with T2DM are asymptomatic and diabetes-related complications are infrequent. Long-term growth hormone therapy does not adversely influence glucose homeostasis in all ages, if weight gain does not occur. Early intervention to prevent obesity and the regular monitoring of glucose levels are recommended in PWS subjects. However, further studies are required to better understand the physiopathological mechanisms of T2DM in these patients.

Prevalence and progression of carbohydrate disorders in patients with pheochromocytoma/paraganglioma: retrospective single-center study.

BACKGROUND: Carbohydrate disorders are the most frequent metabolic disorders, affecting a significant proportion of patients with pheochromocytoma. OBJECTIVE: A retrospective study assessed the prevalence and progression of carbohydrate disorders in 204 patients (92 men, 112 women) with histologically proven pheochromocytoma diagnosed in a single specialized tertiary center during a 40-year period (1978-2017). One hundred were followed-up after tumor removal. RESULTS: Carbohydrate disorders were diagnosed in 49.5% of cases: 30.4% with diabetes and, 19.1% prediabetes. Subjects with carbohydrate disorders had significantly greater age at diagnosis and higher 24-hour urine metanephrine and normetanephrine concentrations than those with normal glucose tolerance. One-third of patients with diabetes achieved good glycemic control under oral treatment (54% on metformin monotherapy). One-third of patients overall required preoperative insulin treatment. Postoperative follow-up (100 patients; 5-year mean duration) showed reduced prevalence of diabetes (13% vs. 33%; P=0.0007) and prediabetes (12% vs. 24%; P=0.027). Almost 60% of subjects initially diagnosed with carbohydrate disorders recovered normal glucose tolerance after surgery; these subjects had significantly higher preoperative urine metanephrine/normetanephrine levels than those with persistent diabetes/prediabetes. Correlation analysis revealed a moderate negative relationship between urine metanephrine/normetanephrine concentration and the outcome of the carbohydrate disorders (Spearmen's Rho=-0.507; P=0.013). There was no significant difference according to pre- or postoperative prevalence of obesity (15% vs. 16%; P=0.845) or dyslipidemia (46% vs. 39%; P=0.316). CONCLUSIONS: Carbohydrate disorders affect approximately 50% of pheochromocytoma patients; 30% develop overt diabetes, which may be the only clinical manifestation in some rare cases. Pheochromocytoma-related diabetes is more likely to affect patients with predominant adrenaline secretion. It is often easy to control and usually requires oral antidiabetic treatment. Reversibility of carbohydrate disorders depend on severity, preoperative metanephrine level, age and weight.

Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice.

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use. EXPERIMENTAL APPROACH: Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice. KEY RESULTS: Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream ß oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells. CONCLUSION AND IMPLICATIONS: Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD.

Glucose metabolism disorders in patients with adrenal gland disorders: pathophysiology and management.

The aim of this review is to explore and discuss disorders of glucose metabolism that can arise in individuals with adrenal gland disorders, as well as to enumerate the available therapeutic treatments for these while considering their benefits and drawbacks. Hyperfunctioning adrenal glands, as in hypercortisolism, hyperaldosteronism, and malignancy, or hypofunctioning of adrenal glands, as in adrenal insufficiency, can lead to carbohydrate metabolism dysregulation with subsequent glucometabolic repercussions, either hyperglycemia or hypoglycemia. Glycemic disorders further affect patients' quality of life and represent a therapeutic dilemma for physicians. Current management strategies for glycemic dysregulation in individuals with adrenal gland disorders are fighting the underlying causes, as well as utilizing antidiabetic therapies that aid in maintaining euglycemia. Further research focused on discovering drug preparations of greater accuracy and effectiveness tailored to patients with adrenal problems as well as studies investigating optimal lifestyle management models for these individuals will assist towards achieving optimal regulation of glucose metabolism.

p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation.

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.

Kisspeptin and Glucose Homeostasis.

Kisspeptin has well-established critical roles in the control of reproduction and fertility. Recently, evidence has emerged that suggests kisspeptin may have additional roles in the regulation of glucose homeostasis. Conflicting reports on the effects of kisspeptin on insulin secretion in animal models have been published, which cannot be fully accounted for by the different kisspeptin isoforms and range of kisspeptin doses used in these studies. Human studies have demonstrated associations between circulating kisspeptin levels and measures of insulin secretion and insulin resistance; and the only published interventional study has confirmed kisspeptin enhances glucose-stimulated insulin secretion in humans. Further studies are required to elucidate the mechanisms underlying the effects of kisspeptin on the pancreatic ß-cell and to determine the therapeutic potential of kisspeptin receptor agonist in the treatment of disorders of glucose homeostasis.

Impaired myocardial deformation and ventricular vascular coupling in obese adolescents with dysglycemia.

BACKGROUND: It is unknown that dysglycemia in obese adolescents has effects on myocardial deformation that are more pronounced when compared to obesity alone. We hypothesized that obesity associated abnormal glucose tolerance (dysglycemia) would have adverse effects on two-dimensional speckle tracking echocardiography derived longitudinal, radial and circumferential strain (LS, RS, CS) compared to age and gender lean controls. We also examined if changes in deformation would be reflected in abnormal ventricular vascular coupling indices (VVI). METHODS: In a prospective cross-sectional design 39 obese adolescents (15.9 ± 1.7 years; 101.5 ± 39 kg; female - 58%) were compared to age and gender matched lean controls (15.7 ± 1.8 yrs, 60 ± 12.8 kg). Based on results from an oral glucose tolerance test (OGTT), obese adolescents were categorized as obese normoglycemic (ONG, n = 25) or obese dysglycemic (ODG, n = 14). Left ventricular (LV) global and average LS, CS, RS and strain rate were measured. LV ejection fraction and mass index were measured and VVI approximated as ratio of arterial elasticity (Ea) and end-systolic elastance (Ees). RESULTS: Adolescents with ODG had significantly (P = 0.005) impaired global LS (- 20.98% ± 2.8%) compared to controls (- 23.01% ± 2.3%). A similar (P = 0.0027) reduction was observed in average LS for adolescents with ODG (18.87% ± 2.5%) compared to controls (20.49% ± 2%). Global CS was also decreased (P = 0.03) in ODG (- 23.95%) compared to ONG (- 25.80). A similar trend was observed in average CS after multivariate regression for BMI and blood pressure. CS correlated with HbA1c in both groups (P = 0.05). VVI had a negative correlation with both LS (r = - 0.4, P = 0.025) and CS rate (r = - 0.36, P = 0.04). CONCLUSIONS: Myocardial strain and strain rate were significantly altered in obese adolescents. Unfavorable subclinical reductions in global and average CS were more pronounced in adolescents with dysglycemia compared to obese adolescents with normoglycemia and controls. These data indicate progressive worsening of subendocardial function across the spectrum of glucose tolerance. Strain rate was predictive of VVI in obese adolescents, suggesting strain rate may be a sensitive marker for cardiac remodeling in abnormal glucose homeostasis states.

Effect of eating resistant starch on the development of overweight, obesity,and disorders of carbohydrate metabolism in children.

Overweight and obesity in children is becoming an increasingly common problem due to the increased access to processed food, overly high energy density diet, and limitation of physical activity in children. Such trends in today's society lead to health consequences that can be observed in the early stages of carbohydrate metabolism disorders. Reduction of body weight and changes in eating habits can prevent the onset of type 2 diabetes. Recently, the benefits of consuming products containing resistant starch, which has the main advantage of influencing the metabolic pathway of glucose, have been increasingly underlined. To date, no recommendations have been made for the daily intake of resistant starch or its content in individual products available on the food market. However, in the medical literature, there are an increasing number of reported cases of the beneficial effect of consuming resistant starch as a factor that supports glycaemic control in children with carbohydrate disorders. Unfortunately, the above topic requires further research in this direction, especially in the developmental age population, which will allow the formulation of precise conclusions regarding its use in the prevention of overweight, obesity, carbohydrate metabolism disorders, and the development of diabetes.

Effect of Konjac Mannan Oligosaccharides on Glucose Homeostasis via the Improvement of Insulin and Leptin Resistance In Vitro and In Vivo.

Functional oligosaccharides, particularly konjac mannan oligosaccharides (KMOS), can regulate glucose metabolism. However, the molecular mechanisms involved in the hypoglycemic effect of KMOS remain largely unknown. Here, the effect of KMOS supplementation on glucose homeostasis was evaluated in both high-fat diet (HFD)-fed C57BL/6J mice and high-glucosamine-induced HepG2 cells. KMOS supplementation remarkably ameliorated the fasting blood glucose, glucose tolerance, and insulin tolerance of HFD-fed mice. Abnormalities of triglyceride and glycogen metabolism in the liver induced by the HFD were reversed by KMOS supplementation. The insulin signaling pathway was activated by KMOS, with stimulation of GLUT2 membrane translocation and glucose uptake in HepG2 cells via the AMPK pathway. Moreover, KMOS suppressed p-mTOR expression and stimulated the GSK-3ß/CREB pathway via the AMPK pathway. KMOS significantly upregulated leptin receptor expression and downregulated PTP1B and SOCS3 levels in the liver and brain, with a decreased serum leptin concentration. Phosphorylation of JAK2 and STAT3 in the liver was activated by KMOS supplementation, while the expressions of Sirt1, Tfam, and Pgc1-α in the brain were elevated. Conclusively, KMOS attenuated HFD-induced glucose metabolism dysfunction through the regulation of insulin resistance and leptin resistance. This finding indicates that KMOS have potential value as an anti-hyperglycemic dietary supplement.

Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults.

BACKGROUND: Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. SUBJECTS AND METHODS: We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2 , hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2 , HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. RESULTS: Obese pubertal youth were more insulin resistant than comparably obese adults (P < .001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤ .05 for group differences). CONCLUSIONS: Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. CLINICAL TRIAL REGISTRATION: The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov.

High birthweight was not associated with altered body composition or impaired glucose tolerance in adulthood.

AIM: To investigate whether a high birthweight was associated with an increased proportion of body fat or with impaired glucose tolerance in adulthood. METHODS: Our cohort comprised 27 subjects with birthweights of 4500 g or more, and 27 controls with birthweights within ±1 standard deviation scores, born at Uppsala University Hospital 1975-1979. The subjects were 34-40 years old at the time of study. Anthropometric data was collected, and data on body composition was obtained by air plethysmography and bioimpedance and was estimated with a three-compartment model. Indirect calorimetry, blood sampling for fasting insulin and glucose as well as a 75 g oral glucose tolerance test were also performed. Insulin sensitivity was assessed using homoeostasis model assessment 2 and Matsuda index. RESULTS: There were no differences in body mass index, body composition or insulin sensitivity between subjects with a high birthweight and controls. CONCLUSION: In this cohort of adult subjects, although limited in size, those born with a moderately high birthweight did not differ from those with birthweights within ±1 standard deviation scores, regarding body composition or glucose tolerance.

Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.

Proopiomelanocortin (POMC) is a key mediator of satiety. Epigenetic marks such as DNA methylation may modulate POMC expression and provide a biological link between early life exposures and later phenotype. Animal studies suggest epigenetic marks at POMC are influenced by maternal energy excess and restriction, prenatal stress and Triclosan exposure. Postnatal factors including energy excess, folate, vitamin A, conjugated linoleic acid and leptin may also affect POMC methylation. Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity. Studies in children propose a link between POMC DNA methylation and elevated lipids and insulin, independent of body habitus. This review brings together evidence from animal and human studies and suggests that POMC is sensitive to nutritional programming and is associated with a wide range of weight-related and metabolic outcomes.