Increase Metabolic Risk Research Articles

Sweet treats before sleep disrupt the clock system and increase metabolic risk markers in healthy rats.

Biological rhythms are endogenously generated natural cycles that act as pacemakers of different physiological mechanisms and homeostasis in the organism, and whose disruption increases metabolic risk. The circadian rhythm is not only reset by light but it is also regulated by behavioral cues such as timing of food intake. This study investigates whether the chronic consumption of a sweet treat before sleeping can disrupt diurnal rhythmicity and metabolism in healthy rats. For this, 32 Fischer rats were administered daily a low dose of sugar (160 mg/kg, equivalent to 2.5 g in humans) as a sweet treat at 8:00 a.m. or 8:00 p.m. (ZT0 and ZT12, respectively) for 4 weeks. To elucidate diurnal rhythmicity of clock gene expression and metabolic parameters, animals were sacrificed at different times, including 1, 7, 13, and 19 h after the last sugar dose (ZT1, ZT7, ZT13, and ZT19). Increased body weight gain and higher cardiometabolic risk were observed when sweet treat was administered at the beginning of the resting period. Moreover, central clock and food intake signaling genes varied depending on snack time. Specifically, the hypothalamic expression of Nampt, Bmal1, Rev-erbα, and Cart showed prominent changes in their diurnal expression pattern, highlighting that sweet treat before bedtime disrupts hypothalamic control of energy homeostasis. These results show that central clock genes and metabolic effects following a low dose of sugar are strongly time-dependent, causing higher circadian metabolic disruption when it is consumed at the beginning of the resting period, that is, with the late-night snack.

Elevated RIF1 participates in the epigenetic abnormalities of zygotes by regulating histone modifications on MuERV-L in obese mice

BackgroundMaternal obesity impairs embryonic developmental potential and significantly increases the risks of metabolic disorders in offspring. However, the epigenetic transmission mechanism of maternal metabolic abnormalities is still poorly understood.MethodsWe established an obesity model in female mice by high-fat diet (HFD) feeding. The effects of the HFD on the developmental potential of oocytes and embryos, the metabolic phenotype, and epigenetic modifications were investigated. The efficacy of metformin administration was assessed. Finally, the regulatory pathway of epigenetic remodeling during zygotic genome activation (ZGA) was explored.ResultsMaternal HFD consumption significantly impaired glucose tolerance and increased the risk of metabolic disorders in F0 and F1 mice. Maternal HFD consumption also decreased embryonic developmental potential, increased reactive oxygen species (ROS) and γH2AX levels, and reduced the mitochondrial membrane potential (MMP) within oocytes, causing high levels of oxidative stress damage and DNA damage. Starting with this clue, we observed significantly increased RIF1 levels and shortened telomeres in obese mice. Moreover, significant abnormal DNA methylation and histone modification remodeling were observed during ZGA in obese mice, which may be coregulated by RIF1 and the ZGA marker gene MuERV-L. Metformin treatment reduced RIF1 levels, and partially improved ZGA activation status by rescuing epigenetic modification remodeling in oocytes and preimplantation embryos of obese mice. RIF1 knockdown experiments employing Trim-Away methods showed that RIF1 degradation altered the H3K4me3 and H3K9me3 enrichment and then triggered the MuERV-L transcriptional activation. Moreover, ChIP-seq data analysis of RIF1 knockouts also showed that RIF1 mediates the transcriptional regulation of MuERV-L by changing the enrichment of H3K4me3 and H3K9me3 rather than by altered DNA methylation.ConclusionElevated RIF1 in oocytes caused by maternal obesity may mediate abnormal embryonic epigenetic remodeling and increase metabolic risk in offspring by regulating histone modifications on MuERV-L, which can be partially rescued by metformin treatment.

Can environmental pollutant bisphenol A increase metabolic risk in polycystic ovary syndrome?

BackgroundBisphenol A (BPA), a widespread industrial substance is recognized as endocrine disrupting chemical and therefore could be associated with polycystic ovary syndrome (PCOS) related metabolic disturbances. PatientsIn this study 29 women of reproductive age with diagnosed PCOS were enrolled. MethodsBPA in urine samples was analyzed by gas chromatography-mass spectrometry. ResultsBPA was detected in urines of 48.28% participants. The waist-to-height ratio (WtHR) was statistically significant higher in PCOS BPA+ in comparison to PCOS BPA− women (p = 0.046). PCOS BPA+ women had 6.88 times (95%Cl 1.3481–35.0600, z = 2.319, p = 0.020) higher risk for waist circumference above 80 cm and 4.95 odds (95%Cl 1.0169–24.096, z = 1.981, p = 0.048) to have WtHR over 0.5 when compared to PCOS BPA−. Statistically significant positive association between BPA urine concentrations and insulin serum levels (p = 0.038) was obtained. BPA urine values were associated with elevated HOMA-IR values and reduced HDL levels with moderate significance (p = 0.079 and p = 0.061, respectively). Also, there was 3.75 times (95%Cl 0.7936–17.7203, z = 1.668, p = 0.095) higher risk for PCOS BPA+ women to have testosterone levels above reference values. ConclusionThe obtained results suggested that the BPA exposition in PCOS women was followed by increased metabolic risk through promotion of obesity, especially the visceral type, hyperinsulinemia, insulin resistance, dyslipidemia and elevated androgen levels.

Lipid alterations in adolescents with early-onset psychosis may be independent of antipsychotic medication

BackgroundDyslipidemia and insulin resistance (HOMA-IR) are cardiovascular risk factors prevalent in patients with psychosis. Whether these factors are intrinsic or affected by lifestyle or antipsychotic medication (AP) is unclear. Therefore, we investigated lipid profiles, HOMA-IR, and psychotic phenotypes in patients aged 12–18 years with early-onset psychosis (EOP) with and without AP exposure. MethodWe measured fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), insulin, and glucose in patients with EOP (n = 39) and healthy controls (HC) (n = 66). Diet information was not available. Negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). We used univariate analysis of variance to compare TC/HDL-C ratios and TG and HOMA-IR values, controlling for body mass index (BMI) and AP exposure. We assessed the explained variance of having EOP using multiple regression analysis. ResultsPatients with and without AP exposure had significantly higher TC/HDL-C (p = 0.003, p = 0.029) and TG values (p < 0.001, p = 0.021) than HC. Significantly increased HOMA-IR scores were found only in AP-exposed patients (p = 0.037). EOP significantly increased the explained variance for TC/HDL-C and TG, but not for HOMA-IR. Patients with a PANSS negative score > 21 had significantly higher levels of TG than those with low scores (p = 0.032). ConclusionOur results suggest that lipid alterations predate AP treatment in adolescents with EOP. Higher levels of negative symptoms and AP further increase metabolic risk. The preliminary findings propose that subclinical dyslipidemia may be intrinsic to EOP.

Promotion of Weight Gain in Early Childhood Does Not Increase Metabolic Risk in Adolescents: A 15-Year Follow-Up of a Cluster-Randomized Controlled Trial1–3

Background: A rapid gain in weight for length may put children at a higher risk of noncommunicable diseases later in life.Objective: The objective of this study was to assess the long-term effects of nutrition counseling delivered in the first 2 y of life in Pelotas, a city in Southern Brazil.Methods: The original cluster-randomized controlled trial was conducted in 1998. Nutrition counseling (breastfeeding promotion and increased intake of micronutrient-rich and energy-dense foods) was delivered to mothers of children aged 0–17.9 mo attending primary care. Six months later, weight gain was higher in the intervention group than in the control group for children ≥12 mo of age at enrollment. In 2013 (mean age 15 y), assessments included anthropometric measurements, body composition (air-displacement plethysmography), body shape (3-dimensional photonic scan), and plasma total, LDL, and HDL cholesterol, triglycerides, C-reactive protein, and glucose.Results: A total of 363 of the 424 original participants were assessed. An a priori decision was made to prioritize analyses of subjects aged 12–17.9 mo at enrollment (51 from the intervention group and 45 from the control group). In this subgroup, boys in the intervention group were [mean (95% CI)] 3.4 (0.8, 6.0) cm taller than those in the control group. Systolic blood pressure tended to be 5.2 (−0.8, 11.1) mm Hg higher in male subjects from the intervention group than in those in the control group. Lipid profiles tended to be healthier in the intervention group. The plasma total cholesterol concentration was −17.8 (−29.8, −5.7) mg/dL lower in boys in the intervention group than in those in the control group. The total-to–HDL cholesterol ratio and triglyceride concentration in the girls in the intervention group were −0.4 (−0.6, −0.1) and −26.3 (−46.3, −6.3) mg/dL, respectively, lower than in the control group. There was no difference between the groups in terms of body composition.Conclusions: Promotion of weight gain in children between 12.0–17.9 mo of age was not associated with higher metabolic risk 15 y later. On the contrary, there was some evidence of reduced metabolic risk in the intervention group.

NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα

Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk. This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques. Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion. These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.

Eating until feeling full and rapid eating both increase metabolic risk factors in Japanese men and women

To investigate the association between eating behaviour and metabolic risk in the broader population. The association between metabolic risk factors (overweight, hypertension, hyperglycaemia, hypertriacylglycerolaemia, low HDL cholesterol, hyperuricaemia and fatty liver) and various eating behaviours were compared for four groups defined by subjective reporting: not eating until feeling full and not eating rapidly (G1); eating until feeling full only (G2); eating rapidly only (G3); and eating both rapidly and until feeling full (G4). A medical centre for health examinations in Tokyo, Japan. Men (n 8240) and women (n 2955) who underwent health examinations. The distribution of participants in G1 to G4 was 49·8 %, 11·5 %, 26·3 % and 12·4 % among men and 55·3 %, 15·0 %, 19·0 % and 10·7 % among women, respectively. Compared with G1, the age-adjusted OR (95 % CI) for overweight were significantly higher in G2 to G4, being respectively 1·85 (1·58, 2·17), 1·98 (1·76, 2·23) and 3·46 (2·99, 4·01) for men and 2·20 (1·62, 2·97), 2·59 (1·97, 3·39) and 3·12 (2·27, 4·26) for women. The age-adjusted OR were also significantly higher for hypertriacylglycerolaemia, hyperuricaemia and fatty liver in G2 and for all risks in G3 and G4 among men; and for hyperuricaemia in G2, for hyperglycaemia, hypertriacylglycerolaemia and fatty liver in G3 and for hypertriacylglycerolaemia and fatty liver in G4 among women. Both eating until feeling full and eating rapidly increase metabolic risk factors. Although the mechanism between rapid eating and metabolic risk requires further exploration, eating slowly and ending meals shortly before feeling full are important public health messages for reducing metabolic risk factors.