Decreased Fat Storage by Lactobacillus Paracasei Is Associated with Increased Levels of Angiopoietin-Like 4 Protein (ANGPTL4)

Background: Intervention strategies for obesity are global issues that require immediate attention. One approach is to exploit the growing consensus that beneficial gut microbiota could be of use in intervention regimes. Our objective was to determine the mechanism by which the probiotic bacteria Lactobacillus paracasei ssp paracasei F19 (F19) could alter fat storage. Angiopoietin-like 4 (ANGPTL4) is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes and has been reported to be regulated by gut microbes. Methodology/Principal Findings: A diet intervention study of mice fed high-fat chow supplemented with F19 was carried out to study potential mechanistic effects on fat storage. Mice given F19 displayed significantly less body fat, as assessed by magnetic resonance imaging, and a changed lipoprotein profile. Given that previous studies on fat storage have identified ANGPTL4 as an effector, we also investigated circulating levels of ANGPTL4, which proved to be higher in the F19-treated group. This increase, together with total body fat and triglyceride levels told a story of inhibited LPL action through ANGPTL4 leading to decreased fat storage. Co-culture experiments of colonic cell lines and F19 were set up in order to monitor any ensuing alterations in ANGPTL4 expression by qPCR. We observed that potentially secreted factors from F19 can induce ANGPTL4 gene expression, acting in part through the peroxisome proliferator activated receptors alpha and gamma. To prove validity of in vitro findings, germ-free mice were monocolonized with F19. Here we again found change

Modelling and optimal control of blood glucose levels in the human body

Regulating the blood glucose level is a challenging control problem for the human body. Abnormal blood glucose levels can cause serious health problems over time, including diabetes. Although several mathematical models have been proposed to describe the dynamics of glucose-insulin interaction, none of them have been universally adopted by the research community. In this paper, we consider a dynamic model of the blood glucose regulatory system originally proposed by Liu and Tang in 2008. This model consists of eight state variables naturally divided into three subsystems: the glucagon and insulin transition subsystem, the receptor binding subsystem and the glucosesubsystem. The model contains 36 model parameters, many of which are unknown and difficult to determine accurately. We formulate an optimal parameter selection problem in which optimal values for the model parameters must be selected so that the resulting model best its given experimental data.We demonstrate that this optimal parameter selection problem can be solved readily using the optimal control software MISER 3.3. Using this approach, significant improvements can be made in matching the model to the experimental data. We also investigate the sensitivity of the resulting optimizedmodel with respect to the insulin release rate. Finally, we use MISER 3.3 to determine optimal open loop controls for the optimized model

Acute effect of meal glycemic index and glycemic load on blood glucose and insulin responses in humans

OBJECTIVE: Foods with contrasting glycemic index when incorporated into a meal, are able to differentially modify glycemia and insulinemia. However, little is known about whether this is dependent on the size of the meal. The purposes of this study were: i) to determine if the differential impact on blood glucose and insulin responses induced by contrasting GI foods is similar when provided in meals of different sizes, and; ii) to determine the relationship between the total meal glycemic load and the observed serum glucose and insulin responses. METHODS: Twelve obese women (BMI 33.7 ± 2.4 kg/m(2)) were recruited. Subjects received 4 different meals in random order. Two meals had a low glycemic index (40–43%) and two had a high-glycemic index (86–91%). Both meal types were given as two meal sizes with energy supply corresponding to 23% and 49% of predicted basal metabolic rate. Thus, meals with three different glycemic loads (95, 45–48 and 22 g) were administered. Blood samples were taken before and after each meal to determine glucose, free-fatty acids, insulin and glucagon concentrations over a 5-h period. RESULTS: An almost 2-fold higher serum glucose and insulin incremental area under the curve (AUC) over 2 h for the high- versus low-glycemic index same sized meals was observed (p < 0.05), however, for the serum glucose response in small meals this was not significant (p = 0.38). Calculated meal glycemic load was associated with 2 and 5 h serum glucose (r = 0.58, p < 0.01) and insulin (r = 0.54, p < 0.01) incremental and total AUC. In fact, when comparing the two meals with similar glycemic load but differing carbohydrate amount and type, very similar serum glucose and insulin responses were found. No differences were observed for serum free-fatty acids and glucagon profile in response to meal glycemic index. CONCLUSION: This study showed that foods of contrasting glycemic index induced a proportionally comparable difference in serum insulin response when provided in both small and large meals. The same was true for the serum glucose response but only in large meals. Glycemic load was useful in predicting the acute impact on blood glucose and insulin responses within the context of mixed meals

Effect of fibre additions to flatbread flour mixes on glucose kinetics:A randomised controlled trial

We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different C-13-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T-50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T-50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production

Estrogen Receptor beta (ERβ) Regulation of Lipid Homeostasis—Does Sex Matter?

In this communication, we aim to summarize the role of estrogen receptor beta (ER&beta;) in lipid metabolism in the main metabolic organs with a special focus on sex differences. The action of ER&beta; is tissue-specific and acts in a sex-dependent manner, emphasizing the necessity of developing sex- and tissue-selective targeting drugs in the future

Glucose appearance in the peripheral circulation and liver glucose output in men after a large 13C starch meal.

International audienceBACKGROUND: Glucose absorption from starchy food has only been described with small amounts ingested ( approximately 20-75 g). OBJECTIVE: Our aim was to describe total plasma (Ra) and exogenous glucose (Ra(exo)) appearance, glucose release from the liver (HGP), and the metabolic response after ingestion of 5 g polished or parboiled rice/kg body mass. DESIGN: Gas exchange and urea excretion were monitored in 8 healthy subjects before (3.5 h) and after (8 h) ingestion of rice intrinsically labeled with (13)C; [6,6-(2)H(2)]glucose was infused for the measurement of Ra, Ra(exo), and HGP. RESULTS: Changes in plasma glucose, insulin, lactate, and free fatty acids and the increase in Ra(exo) and Ra ( approximately 200%) and the decrease in HGP ( approximately 90%) were not significantly different (P > 0.05) after ingestion of either rice. Glucose oxidation was not significantly different (111.6 +/- 8.2 compared with 89.0 +/- 11.3 g; P = 0.13), but fat oxidation was significantly lower (9.9 +/- 1.7 compared with 21.3 +/- 4.0 g; P 0.05). CONCLUSION: Although the starch in parboiled rice is less susceptible to digestion in vitro, exogenous glucose availability was not significantly different after ingestion of large amounts of polished or parboiled rice. Glucose absorption remains incomplete 8 h after ingestion of both types of rice

Relationship between visceral adiposity and intramyocellular lipid content in two rat models of insulin resistance.

High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels was explored in diet- and glucocorticoid-induced models of insulin resistance. In the diet-induced model, lean and fa/fa Zucker rats were fed either normal or high-fat (HF) chow over 4 wk. Fat distribution, IMCL content in the tibialis anterior (TA) muscle (IMCL(TA)), and whole body insulin resistance were measured before and after the 4-wk period. The HF diet-induced increase in IMCL(TA) was strongly correlated with visceral fat accumulation and greater glucose intolerance in both groups. The increase in IMCL(TA) to visceral fat accumulation was threefold greater for fa/fa rats. In the glucocorticoid-induced model, insulin sensitivity was impaired with dexamethasone. In vivo adiposity and IMCL(TA) content measurements were combined with ex vivo analysis of plasma and muscle tissue. Dexamethasone treatment had minimal effects on visceral fat accumulation while increasing IMCL(TA) levels approximately 30% (P < 0.05) compared with controls. Dexamethasone increased plasma glucose by twofold and increased the saturated fatty acid content of plasma lipids [fatty acid (CH2)n/omegaCH3 ratio +15%, P < 0.05]. The lipid composition of the TA muscle was unchanged by dexamethasone treatment, indicating that the relative increase in IMCL(TA) observed in vivo resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL accumulation in the context of dietary manipulations; however, a "causal" relationship still remains to be determined. Dexamethasone-induced insulin resistance likely operates under a different mechanism, i.e., independently of visceral adiposity

Glucose appearance in the peripheral circulation and liver glucose output in men after a large 13C starch meal.

International audienceBACKGROUND: Glucose absorption from starchy food has only been described with small amounts ingested ( approximately 20-75 g). OBJECTIVE: Our aim was to describe total plasma (Ra) and exogenous glucose (Ra(exo)) appearance, glucose release from the liver (HGP), and the metabolic response after ingestion of 5 g polished or parboiled rice/kg body mass. DESIGN: Gas exchange and urea excretion were monitored in 8 healthy subjects before (3.5 h) and after (8 h) ingestion of rice intrinsically labeled with (13)C; [6,6-(2)H(2)]glucose was infused for the measurement of Ra, Ra(exo), and HGP. RESULTS: Changes in plasma glucose, insulin, lactate, and free fatty acids and the increase in Ra(exo) and Ra ( approximately 200%) and the decrease in HGP ( approximately 90%) were not significantly different (P > 0.05) after ingestion of either rice. Glucose oxidation was not significantly different (111.6 +/- 8.2 compared with 89.0 +/- 11.3 g; P = 0.13), but fat oxidation was significantly lower (9.9 +/- 1.7 compared with 21.3 +/- 4.0 g; P 0.05). CONCLUSION: Although the starch in parboiled rice is less susceptible to digestion in vitro, exogenous glucose availability was not significantly different after ingestion of large amounts of polished or parboiled rice. Glucose absorption remains incomplete 8 h after ingestion of both types of rice

High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner

There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ERβ) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ERα-selective activation reduced body weight and generated systemic effects, whereas ERβ-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.QC 20201009</p