Body Insulin Sensitivity Research Articles

Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet.

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

Separate and combined relationships for cardiorespiratory fitness and muscular strength with visceral fat and insulin sensitivity in adolescents with obesity.

We examined the separate and combined associations for cardiorespiratory fitness (CRF) and muscular strength (MS) with total and regional fat, and insulin sensitivity (IS) in 204 adolescents (BMI ≥85th percentile, 12-18 years) at UPMC Children's Hospital of Pittsburgh. CRF was measured by maximum oxygen consumption during a graded treadmill test. MS was quantified by combining 1-repetition maximum test for the leg and bench press. Participants were stratified as having either high or low CRF and MS based on sex-specific median split. Both high CRF and high MS groups had lower (P < 0.05) total fat after adjustment for sex, Tanner stage and ethnicity than the low CRF and MS groups (Difference: 6.6, 2.6-9.6% and 5.4, 2.4-8.3%, respectively). High CRF, but not high MS, had lower visceral (67.5 versus 77.9 cm2, P < 0.01) and intermuscular fat (3.6 versus 4.0 kg, P = 0.01) than the low CRF groups. Differences by CRF remained significant after adjustment for MS. High CRF, but not high MS, was associated (P < 0.05) with lower fasting glucose and higher IS after accounting for sex, Tanner stage and ethnicity than the low CRF group, and high CRF remained associated with these markers after adjustment for MS. High CRF is associated with lower total and regional fat, and higher IS after adjustment for MS. Novelty: CRF is associated with lower total fat, visceral and intermuscular fat, and higher insulin sensitivity adjusting for muscular strength. Muscular strength is not associated with regional body fat and insulin sensitivity after accounting for CRF.

Adult mice are unresponsive to AAV8-Gremlin1 gene therapy targeting the liver.

ObjectiveGremlin 1 (GREM1) is a secreted BMP2/4 inhibitor which regulates commitment and differentiation of human adipose precursor cells and prevents the browning effect of BMP4. GREM1 is an insulin antagonist and serum levels are high in type 2 diabetes (T2D). We here examined in vivo effects of AAV8 (Adeno-Associated Viral vectors of serotype eight) GREM 1 targeting the liver in mature mice to increase its systemic secretion and also, in a separate study, injected recombinant GREM 1 intraperitoneally. The objective was to characterize systemic effects of GREM 1 on insulin sensitivity, glucose tolerance, body weight, adipose cell browning and other local tissue effects.MethodsAdult mice were injected with AAV8 vectors expressing GREM1 in the liver or receiving regular intra-peritoneal injections of recombinant GREM1 protein. The mice were fed with a low fat or high fat diet (HFD) and followed over time.ResultsLiver-targeted AAV8-GREM1 did not alter body weight, whole-body glucose and insulin tolerance, or adipose tissue gene expression. Although GREM1 protein accumulated in liver cells, GREM1 serum levels were not increased suggesting that it may not have been normally processed for secretion. Hepatic lipid accumulation, inflammation and fibrosis were also not changed. Repeated intraperitoneal rec-GREM1 injections for 5 weeks were also without effects on body weight and insulin sensitivity. UCP1 was slightly but significantly reduced in both white and brown adipose tissue but this was not of sufficient magnitude to alter body weight. We validated that recombinant GREM1 inhibited BMP4-induced pSMAD1/5/9 in murine cells in vitro, but saw no direct inhibitory effect on insulin signalling and pAkt (ser 473 and thr 308) activation.ConclusionGREM1 accumulates intracellularly when overexpressed in the liver cells of mature mice and is apparently not normally processed/secreted. However, also repeated intraperitoneal injections were without effects on body weight and insulin sensitivity and adipose tissue UCP1 levels were only marginally reduced. These results suggest that mature mice do not readily respond to GREMLIN 1 but treatment of murine cells with GREMLIN 1 protein in vitro validated its inhibitory effect on BMP4 signalling while insulin signalling was not altered.

Genetic ablation of C-reactive protein gene confers resistance to obesity and insulin resistance in rats.

Besides serving as a traditional inflammatory marker, C-reactive protein (CRP) is closely associated with the development of obesity, diabetes and cardiovascular diseases as a metabolic and inflammatory marker. We hypothesise that CRP protein directly participates in the regulation of energy and glucose metabolism rather than just being a surrogate marker, and that genetic deficiency of CRP will lead to resistance to obesity and insulin resistance. Crp gene deletion was achieved by transcription activator-like effector nuclease (TALEN) technology in rats. The Crp knockout animals were placed on either a standard chow diet or a high-fat diet. Phenotypic changes in body weight, glucose metabolism, insulin sensitivity, energy expenditure and inflammation condition were examined. The central impact of CRP deficiency on leptin and insulin hypothalamic signalling, as well as glucose homeostasis, were examined via intracerebral ventricular delivery of leptin and CRP plus glucose clamp studies in the wild-type and Crp knockout rats. CRP deficiency led to a significant reduction in weight gain and food intake, elevated energy expenditure and improved insulin sensitivity after exposure to high-fat diet. Glucose clamp studies revealed enhanced hepatic insulin signalling and actions. Deficiency of CRP enhanced and prolonged the weight-reducing effect of central injected leptin and promoted the central and peripheral roles of leptin. By contrast, reinstatement of CRP into the hypothalamus of the knockout rats attenuated the effects of central leptin signalling on insulin sensitivity and peripheral glucose metabolism. This study represents the first line of genetic evidence that CRP is not merely a surrogate blood marker for inflammation and metabolic syndromes but directly regulates energy balance, body weight, insulin sensitivity and glucose homeostasis through direct regulation of leptin's central effect and hypothalamic signalling.

A Mediterranean Diet and Low-Fat Vegan Diet to Improve Body Weight and Cardiometabolic Risk Factors: A Randomized, Cross-over Trial

Objective: Evidence suggests that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but their relative efficacy has not been compared in a randomized trial. Methods: In a randomized crossover trial, 62 overweight adults were randomly assigned to a Mediterranean or vegan diet for a 16-week period. Body weight, plasma lipids, blood pressure, and body composition (dual X-ray absorptiometry) were measured. Secondary measures included insulin resistance (Homeostasis Model Assessment, HOMA-IR), oral glucose insulin sensitivity (OGIS), and predicted insulin sensitivity (PREDIM) indices. Thereafter, participants were asked to return to their baseline diets for 4 weeks, after which they began the opposite diet for 16 weeks. The same parameters were measured before and after this 2nd 16-week period. Results: Overall net weight changes were 0.0 (Mediterranean) and −6.0 kg (vegan), (treatment effect −6.0 kg [95% CI −7.5 to −4.5]; p < 0.001). HOMA-IR decreased and OGIS increased on the vegan diet with no significant change on the Mediterranean diet (treatment effect −0.7 [95% CI, −1.8 to +0.4]; p = 0.21; and +35.8 mL/min/m2 [95% CI, +13.2 to +58.3]; p = 0.003, respectively). PREDIM did not change significantly in either group. Among participants with no medication changes, total and LDL-cholesterol decreased 18.7 mg/dL (0.5 mmol/L) and 15.3 mg/dL (0.4 mmol/L), respectively, on the vegan diet, compared with no significant change on the Mediterranean diet (treatment effect −15.6 [-24.6 to −6.6]; p = 0.001 and −14.8 [-23.5 to −6.2]; p = 0.001, respectively); systolic and diastolic blood pressure decreased 9.3 and 7.3 mmHg on the Mediterranean diet, compared with 3.4 and 4.1 mmHg on the vegan diet (treatment effect +5.9 [95% CI +1.0 to +10.9]; p = 0.02; and +1.8 [95% CI −4.6 to +8.1]; p = 0.58, respectively). Conclusions: A low-fat vegan diet improved body weight, lipid concentrations, and insulin sensitivity, both from baseline and compared with a Mediterranean diet. Blood pressure decreased on both diets, more on the Mediterranean diet. Clinical trial registration: ClinicalTrials.gov number, NCT03698955 https://clinicaltrials.gov/ct2/show/NCT03698955?term=NCT03698955&draw=2&rank=1

Olanzapine-induced insulin resistance may occur via attenuation of central KATP channel-activation

Antipsychotic use is associated with an increased risk of type 2 diabetes. Recent work suggests antipsychotics can induce insulin resistance immediately and independently of weight gain, and that this may occur via the central nervous system (CNS). We have previously shown that the highly effective and widely prescribed antipsychotic, olanzapine inhibits CNS insulin-mediated suppression of hepatic glucose production, but the mechanisms remain unknown. The ATP-sensitive potassium (KATP) channel is a key metabolic sensor downstream of hypothalamic insulin signalling, involved in the maintenance of glucose homeostasis. Thus, the possibility arises that olanzapine inhibits central KATP channel activation to disrupt glucose metabolism. We replicate that intracerebroventricular (ICV) administration of the KATP channel activator, diazoxide, suppresses hepatic glucose production and additionally demonstrate stimulation of peripheral glucose utilization. We report that olanzapine inhibits the effects of central KATP channel activation resulting in perturbation of whole body insulin sensitivity, specifically via inhibition of glucose utilization, while leaving central KATP channel-mediated suppression of glucose production intact. Perturbation of KATP channel action in the CNS could represent a novel mechanism of antipsychotic-induced diabetes.

Empagliflozin therapy and insulin resistance-associated disorders: effects and promises beyond a diabetic state.

Empagliflozin is a SGLT2 inhibitor that has shown remarkable cardiovascular and renal activities in patients with type 2 diabetes (T2D). Preclinical and clinical studies of empagliflozin in T2D population have demonstrated significant improvements in body weight, waist circumference, insulin sensitivity, and blood pressure – effects beyond its antihyperglycaemic control. Moreover, several studies suggested that this drug possesses significant anti-inflammatory and antioxidative stress properties. This paper explores extensively the main preclinical and clinical evidence of empagliflozin administration in insulin resistance-related disorders beyond a diabetic state. It also discusses its future perspectives, as a therapeutic approach, in this high cardiovascular-risk population.

The Relationship Between Thyroid Function and Body Composition, Leptin, Adiponectin, and Insulin Sensitivity in Morbidly Obese Euthyroid Subjects Compared to Non-obese Subjects.

Background/Objectives:Thyroid function tests (TFTs) changes in obese people have been studied with increasing interest, however, studies have been inconsistent hence it remains poorly understood. We compared the TFTs of morbidly obese euthyroid Saudi subjects with non-obese controls and then we examined the influence of leptin, adiponectin, and insulin resistance on TFTs.Subjects/Methods:Fifty-five euthyroid obese subjects attending bariatric surgery clinic and 52 non-obese age-and gender-matched controls were recruited. We measured body weight, BMI, body composition, thyroid-stimulating hormone (TSH), Free T4 (FT4), Free T3(FT3), thyroid antibodies, fasting leptin, adiponectin, and lipid profile. Insulin resistance was quantified by HOMA-IR. Data are presented as mean ± SEM.Results:Mean BMI was 45.6 ± 1.5 and 23.2 ± 0.5 kg/m2, for the obese and non-obese controls, respectively, P value < 0.001. Mean TSH was 2.7 ± 0.18 mIU/L in obese subjects and 1.7 ± 0.13 mIU/L (0.27-4.2) in the non-obese controls, respectively, P value .014. Mean FT3 was 3.9 ± 0.1 pmol/L (3.1-6.8) in obese subjects compared to 5.0 ± 0.1 pmol/L in non-obese controls, respectively, P value 0.001, however, FT4 was similar in the 2 groups. In the whole group (N = 107), BMI correlated positively with TSH and negatively with FT3. Leptin correlated negatively with both FT4 and FT3 in the non-obese group only while none of the TFTs correlated with HOMA-IR or adiponectin in either group. Binary logistic regression showed that each 1 unit increase in TSH increased the odds of becoming obese by 12.7, P value 0.009, 95 C.I. (1.9-85.0). Conversely, each - unit increase in FT3 decreased the odds of becoming obese by 0.2, P value 0.023, 95% C.I. (0.05-0.80).Conclusions:We report a small increase in TSH and a small decrease in FT3 within the normal range in obese subjects compared to non-obese controls. We also report a positive correlation between TSH and BMI with increased odds ratio of becoming obese with the increase in TSH and decrease in FT3. These changes may be either causally related or adaptive to the obesity state. FT4 and FT3 seem to correlate with leptin (but not with adiponectin or HOMA-IR) in the non-obese controls only. Larger mechanistic studies are needed to further elucidate the interesting association between obesity and TFTs.

PSVIII-40 Late-Breaking Abstract: Variability in body composition is associated with insulin sensitivity in growing-finishing pigs

Abstract Growing pigs’ body composition variation can be associated with differences in insulin sensitivity given the insulin anabolic effect on protein and lipid synthesis. The objective of this study was to elucidate this association by relating the individual insulin response to the oral glucose tolerance test (OGTT) with the body composition of growing pigs. Thirty 95 kg jugular vein catheterized pigs received an oral dose of 1.75 g of glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 min following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. Body lipids (LB, %) and protein (PB, %) composition were estimated by dual X-ray densitometry. Association between body composition and insulin sensitivity were studied by using partial least squares and correlations. Average LB and PB were 19.7% (CV = 7.6 %) and 16.2% (CV = 2.2%), respectively. Basal insulin blood concentration and area-under-the-curve (AUC) CV (51.9 % and 26.9 %, respectively) were larger than those for basal glucose and AUC (5.52 and 5.48 %, respectively). Additionally, insulin sensitivity (%S), steady-state beta cell function (%B), and insulin resistance (HOMA-IR) estimated with the Homeostasis Model Assessment (HOMA 2) and whole-body insulin sensitivity index (ISI) were highly variable between pigs which CV ranged from 30.1 % to 54.5 %. These results can indicate an early stage of insulin resistance in an important part of the studied pig population. LB and PB were affected by insulin sensitivity indexes (P &amp;lt; 0.05) which accounted, respectively, for 48% and 44% of the observed variation. In conclusion, lower insulin sensitivity was associated with higher body fat in growing pigs raised under similar conditions.

Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults

Excess body weight and insulin resistance lead to type 2 diabetes and other major health problems. There is an urgent need for dietary interventions to address these conditions. To measure the effects of a low-fat vegan diet on body weight, insulin resistance, postprandial metabolism, and intramyocellular and hepatocellular lipid levels in overweight adults. This 16-week randomized clinical trial was conducted between January 2017 and February 2019 in Washington, DC. Of 3115 people who responded to flyers in medical offices and newspaper and radio advertisements, 244 met the participation criteria (age 25 to 75 years; body mass index of 28 to 40) after having been screened by telephone. Participants were randomized in a 1:1 ratio. The intervention group (n = 122) was asked to follow a low-fat vegan diet and the control group (n = 122) to make no diet changes for 16 weeks. At weeks 0 and 16, body weight was assessed using a calibrated scale. Body composition and visceral fat were measured by dual x-ray absorptiometry. Insulin resistance was assessed with the homeostasis model assessment index and the predicted insulin sensitivity index (PREDIM). Thermic effect of food was measured by indirect calorimetry over 3 hours after a standard liquid breakfast (720 kcal). In a subset of participants (n = 44), hepatocellular and intramyocellular lipids were quantified by proton magnetic resonance spectroscopy. Repeated measure analysis of variance was used for statistical analysis. Among the 244 participants in the study, 211 (87%) were female, 117 (48%) were White, and the mean (SD) age was 54.4 (11.6) years. Over the 16 weeks, body weight decreased in the intervention group by 5.9 kg (95% CI, 5.0-6.7 kg; P < .001). Thermic effect of food increased in the intervention group by 14.1% (95% CI, 6.5-20.4; P < .001). The homeostasis model assessment index decreased (-1.3; 95% CI, -2.2 to -0.3; P < .001) and PREDIM increased (0.9; 95% CI, 0.5-1.2; P < .001) in the intervention group. Hepatocellular lipid levels decreased in the intervention group by 34.4%, from a mean (SD) of 3.2% (2.9%) to 2.4% (2.2%) (P = .002), and intramyocellular lipid levels decreased by 10.4%, from a mean (SD) of 1.6 (1.1) to 1.5 (1.0) (P = .03). None of these variables changed significantly in the control group over the 16 weeks. The change in PREDIM correlated negatively with the change in body weight (r = -0.43; P < .001). Changes in hepatocellular and intramyocellular lipid levels correlated with changes in insulin resistance (both r = 0.51; P = .01). A low-fat plant-based dietary intervention reduces body weight by reducing energy intake and increasing postprandial metabolism. The changes are associated with reductions in hepatocellular and intramyocellular fat and increased insulin sensitivity. ClinicalTrials.gov Identifier: NCT02939638.

Impact of Lean Body Mass and Insulin Sensitivity on the IGF-1-Bone Mass Axis in Adolescence: the EPICOM Study.

Insulin-like growth factor-1 (IGF-1) is involved in the growth of muscle and bone mass and contributes to glucose homeostasis. The offspring of mothers with diabetes during pregnancy have an increased risk of insulin resistance (IR). We hypothesized that bone mass was decreased in the offspring of mothers with type 1 diabetes (T1D), and that the IGF-1-bone mass relationship would be negatively influenced by IR. Data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) study performed from 2012 to 2013 were included. This work is a follow-up study of a nationwide register study. A total of 278 adolescent index offspring whose mothers had T1D and 303 matched controls were studied. Bone mineral content (BMC) determined by a dual-energy x-ray absorptiometry scan and the interaction with IGF-1 and insulin sensitivity were measured. There was no difference in BMC, bone mineral density, height (SD score [SDS]), or BMC/height between index and control offspring. IGF-1 (SDS) did not differ between the groups but insulin-like growth factor-binding protein 3 (SDS) was higher in index boys compared to controls (B = .31 [95% CI, 0.06-0.57], P = .02). The statistical path analysis showed that IGF-1 predicted BMC/height (B = .24 [95% CI, 0.02-0.45], P = .03), but lean mass was a mediator of this. IGF-1 and the homeostatic model assessment of IR were positively associated (B = .75 [95% CI, 0.37-1.12], P < .001). There was no moderating effect of the interaction between IR and IGF-1 on lean mass in the entire cohort (B = .005 [95% CI, -0.03 to 0.04], P = .81) or when analyzing index cases and controls separately. We found that lean mass was an intermediary factor in the IGF-1-bone mass relationship in a large cohort of adolescents, and this relationship was not moderated by IR.

O11 La menor cantidad de horas semanas de actividad se asocia a alteraciones del metabolismo de la glucosa en niños y adolescentes obesos mendocinos

Introducción: el sedentarismo ha emergido como un factor de riesgo independiente en la población pediátrica. Se asocia al síndrome metabólico, a la alteración de la composición corporal y disminución del rendimiento académico, pero no se ha aclarado su relación con alteraciones de la glucemia.Objetivos: evaluar la relación entre la cantidad semanal de actividad desarrollada y las alteraciones del metabolismo de la glucosa en niños y adolescentes obesos.Materiales y métodos: se estudiaron 78 pacientes obesos separados en cuartilos de actividad programada y espontánea. Se obtuvieron score z-IMC, índice cintura/talla, presión arterial (TAS y TAD), masa grasa y magra por densitometría, adiponectina, miostatina, parámetros metabólicos en ayunas (glucemia, HOMA-IR) y durante la PTOG: áreas bajo la curva (ABC), sensibilidad insulínica (SI) corporal total (Matsuda), hepática y muscular (DeFronzo), índice de disposición de glucosa (IDG) y frecuencia de AGA, ITG y diabetes. Se utilizaron t de Student, Anova con transformación logarítmica, X2 y Odd Ratios para comparar grupos, frecuencias y probabilidad de alteraciones metabólicas.

O12 La obesidad de inicio temprano se asocia a mayor peso al nacer, hábitos sedentarios y a los componentes del síndrome metabólico pediátrico

Introducción: las complicaciones de la obesidad aparecen precozmente en niños. Su frecuencia varía con la severidad del acúmulo graso y su distribución. El peso al nacer (PN), el inicio temprano del sobrepeso y el sedentarismo podrían agravar el riesgo metabólico.Objetivos: determinar los factores que se relacionan con la severidad de la obesidad y presencia de componentes del síndrome metabólico pediátrico.Materiales y métodos: se estudiaron 78 pacientes de 5-15 años con sobrepeso de grado variable. Se obtuvieron: PN, puntaje de actividad (escala de Godard), score z-IMC, índice cintura/talla, percentilo de presión arterial (TAS y TAD), masa grasa y magra por densitometría, glucemia, lípidos, transaminasas, PCR, insulinemia, péptido C, HOMA-adiponectina, sensibilidad insulínica (SI) corporal total (Matsuda) y muscular (DeFronzo), a partir de la prueba de tolerancia a la glucosa. Se utilizaron Anova, X2 y Mann-Whitney para comparar grupos, frecuencias y variables no normales.

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest.

Background: Fetuin-A is a hepatokine linked to the development of insulin resistance. The purpose of this study was to determine if 60 days head-down-tilt (HDT) bed rest increased circulating fetuin-A and if it was linked to whole body insulin sensitivity (IS). Additionally, we examined whether reactive jump training (RJT) could alleviate the metabolic changes associated with bed rest.Methods: 23 young men (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were randomized to a control (CTRL, n = 11) or RJT group (JUMP, n = 12) and exposed to 60 days of bed rest. Before and after bed rest, body composition and were measured and an oral glucose tolerance test was performed to estimate IS. Circulating lipids and fetuin-A were measured in fasting serum.Results: Body weight, lean mass, and decreased in both groups following bed rest, with greater reductions in CTRL (p < 0.05). There was a main effect of time, but not the RJT intervention, for the increase in fetuin-A, triglycerides (TG), area under the curve for glucose (AUCG) and insulin (AUCI), and the decrease in Matsuda and tissue-specific IS (p < 0.05). Fetuin-A increased in participants who became less insulin sensitive (p = 0.019). In this subgroup, liver IS and adipose IS decreased (p < 0.05), while muscle IS was unchanged. In a subgroup, where IS did not decrease, fetuin-A did not change. Liver IS increased (p = 0.012), while muscle and adipose tissue IS remained unchanged.Conclusions: In this study, we report an increase in circulating fetuin-A following 60 days of bed rest, concomitant with reduced IS, which could not be mitigated by RJT. The amount of fetuin-A released from the liver may be an important determinant of changes in whole body IS. In this regard, it may also be a useful biomarker of individual variation due to inactivity or lifestyle interventions.

Effects of descending or ascending stair exercise on body composition, insulin sensitivity, and inflammatory markers in young Chinese women with obesity: A randomized controlled trial

ABSTRACT We examined the effects of descending (DSE) or ascending (ASE) stair exercise on body composition, insulin sensitivity, and inflammatory markers in young Chinese women with obesity. Thirty-six participants were randomly assigned into three groups DSE, ASE and a control group. The DSE and ASE groups performed three sessions of stair walking per week for 12 weeks with a gradual increase in repetitions. Following the exercise interventions, body composition related variables obtained by Dual-energy X-ray absorptiometry scans significantly decreased. Abdominal fat decreased in the DSE group only. Moreover, Insulin sensitivity improved significantly 3.5-fold in the DSE group compared with ASE group (insulin: −33.2% vs. −9.8%, homoeostasis model assessment for insulin resistance: −35.6% vs. −10.8%). Pro-inflammatory factors showed significant decreases in tumour necrosis factor-α (TNF-α) (−39.9% vs. −23.2%) for both intervention groups. The reduction in TNF-α concentrations in the DSE group was significantly different compared to the other two groups. Interleukin-6 significantly decreased in both exercise protocols. Our results show that 12-weeks induced stair walking improved body composition parameters in Chinese females with obesity. The results also demonstrate the superiority of the DSE protocol for improving insulin sensitivity. These findings may be attributable to the decreases observed in TNF- α levels.

Simulated shift work during pregnancy does not impair progeny metabolic outcomes in sheep.

Maternal shift work increases the risk of pregnancy complications, although its effects on progeny health after birth are not clear. We evaluated the impact of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on the metabolic health of sheep progeny. Simulated shift work had no effect on growth, body size, body composition or glucose tolerance in pre-pubertal or young adult progeny. Glucose-stimulated insulin secretion was reduced in adult female progeny and insulin sensitivity was increased in adult female singleton progeny. The results of the present study do not support the hypothesis that maternal shift work exposure impairs metabolic health of progeny in altricial species. Disrupted maternal circadian rhythms, such as those experienced during shift work, are associated with impaired progeny metabolism in rodents. The effects of disrupted maternal circadian rhythms on progeny metabolism have not been assessed in altricial, non-litter bearing species. We therefore assessed postnatal growth from birth to adulthood, as well as body composition, glucose tolerance, insulin secretion and insulin sensitivity, in pre-pubertal and young adult progeny of sheep exposed to control conditions (CON: 10males, 10 females) or to a simulated shift work (SSW) protocol for the first one-third (SSW0-7: 11males, 9 females), the first two-thirds (SSW0-14: 8males, 11 females) or all (SSW0-21: 8males, 13 females) of pregnancy. Progeny growth did not differ between maternal treatments. In pre-pubertal progeny (12-14weeks of age), adiposity, glucose tolerance and insulin secretion during an i.v. glucose tolerance test and insulin sensitivity did not differ between maternal treatments. Similarly, in young adult progeny (12-14months of age), food intake, adiposity and glucose tolerance did not differ between maternal treatments. At this age, however, insulin secretion in response to a glucose bolus was 30% lower in female progeny in the combined SSW groups compared to control females (P=0.031), and insulin sensitivity of SSW0-21singleton females was 236% compared to that of CON singleton female progeny (P=0.025). At least in this model, maternal SSW does not impair progeny metabolic health, with some evidence of greater insulin action in female young adult progeny.

Exercise ameliorates insulin resistance and improves SIRT6-mediated insulin signaling transduction in liver of obese rats.

Physical exercise is essential for the amelioration of insulin resistance (IR). The mechanisms in charge of improved IR, regulated by exercise, are insufficiently studied. Previous research revealed that Sirtuin 6 (SIRT6) - mediated insulin signaling acts a crucial element in hepatic IR. The objective of our research was to determine the effects of exercise on SIRT6-mediated insulin signaling in liver of IR rats. Forty male Sprague Dawley rats were randomly assigned to four groups (n = 10 rats each): control rats fed with standard chow (Lean group); sedentary rats fed with a high-fat diet (HFD-SED); rats fed with HFD and submitted to 8 week chronic swimming exercise training (HFD-CE); and rats fed HFD and submitted to one acute swimming exercise training (HFD-AE). HFD feeding lead to increased body weight, accumulation of hepatic triglyceride and serum free fatty acids, and enhanced gluconeogenesis. Besides, HFD feeding decreased body insulin sensitivity. Hepatic USP10 and SIRT6 protein levels decreased under obese status. Both chronic and acute exercise intervention alleviated physiological and metabolic status, increased hepatic USP10 and SIRT6 levels, improved insulin signaling transduction, and inhibited gluconeogenesis. These results showed that exercise intervention regulated SIRT6-mediated insulin signaling, which contributes to our understanding of the molecular mechanisms behind IR, in that a regular exercise can mitigate the effects of IR.

Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome

ObjectiveIncreasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown. MethodsWe compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on (123I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points. ResultsWe observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression. ConclusionsAlthough more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated. NTR registration4488.

A Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth

ABSTRACTBackgroundRecent literature suggests that the Western diet's imbalance between high ω-6 (n–6) and low ω-3 (n–3) PUFA intake contributes to fatty liver disease in obese youth.ObjectivesWe tested whether 12 wk of a low n–6:n–3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response.MethodsIn a single-arm unblinded study, obese youth 9–19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n–6:n–3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann–Whitney U test, and covariance pattern modeling were used.ResultsTwenty obese adolescents (median age: 13.3 y; IQR: 10.5–16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time.ConclusionsThese data suggest that, independently of weight loss, a low n–6:n–3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.

Body composition, insulin sensitivity and blood pressure in patients with congenital adrenal hyperplasia

Body composition, insulin sensitivity and blood pressure in patients with congenital adrenal hyperplasia