Influence of Brown or Germinated Brown Rice Supplementation on Fecal Short-Chain Fatty Acids and Microbiome in Diet-Induced Insulin-Resistant Mice.

Intake of whole grain foods is associated with improving metabolic profile compared to refined grain products, but the underlying mechanism remains unclear. The present study examined the effects of brown rice (BRR) or germinated brown rice (GBR) supplementation on fecal short-chain fatty acids (SCFAs), and relationship with gut microbiota, metabolism and inflammation in high fat (HF)-diet-fed mice. The results demonstrated that an HF diet supplemented with BRR or GBR comparably increased the abundance of fecal isobutyric acid compared to that in mice receiving HF+white rice (WHR) diet (p < 0.01). The abundance of valeric acid in HF+GBR-diet-fed mice was higher than those receiving HF+WHR diet (p < 0.05). The abundances of fecal isobutyric acid negatively correlated with fasting plasma glucose, insulin, cholesterol, triglycerides, tumor necrosis factor-α, plasminogen activator inhibit-1, monocyte chemotactic protein-1 and homeostatic model assessment of insulin resistance (p < 0.01). The abundance of valeric acids negatively correlated with insulin resistance (p < 0.05). The abundances of isobutyric acid positively correlated with Lactobacillus, but negatively correlated with Dubosiella genus bacteria (p < 0.05). The findings demonstrated that the increases in SCFAs in the feces of BRR and GBR-treated mice were associated with improvements in gut microbiome, metabolic and inflammatory profile, which may contribute to the antidiabetic and anti-inflammatory effects of the whole grains in HF-diet-fed mice.

Special Issue "Nutritional Regulation on Gut Microbiota": Editorial.

Accumulated lines of evidence demonstrate that the gut microbiota plays a critical role in metabolism, inflammation and the pathophysiology of many chronic diseases [...].

SmartMoms Canada: An evaluation of a mobile app intervention to support a healthy pregnancy.

BACKGROUND: There is a lack of cost-effective and readily available access to evidence-based information to manage healthy behaviours for pregnant individuals. Mobile health (mHealth) tools offer a cost-effective, interactive, personalized option that can be delivered anywhere at a time most convenient for the user. This study protocol was primarily developed to, i) assess the feasibility of the SmartMoms Canada intervention in supporting participants to achieve gestational weight gain (GWG) guidelines. The secondary objectives are to, ii) assess user experience with the app, measured by adherence to the program via app software metrics and frequency of use, iii) determine the impact of SmartMoms Canada app usage on the adoption of healthful behaviours related to nutrition, physical activity and sleep habits, improvements in health-related quality of life, pregnancy-related complications, and symptoms of depression, and iv) investigate the potential extended effects of the app on postpartum health-related outcomes. METHODS: This is a feasibility trial. Pregnant individuals aged 18-40 years with pre-gravid body mass index between 18.5 and 39.9 kg/m2, carrying a singleton fetus, having Wi-Fi access, and at ≤20 weeks' gestation will be recruited. Eligible people will be followed from recruitment until 12 months postpartum. DISCUSSION: SmartMoms Canada is the first bilingual Canadian-centric app designed for pregnant people. This mHealth intervention, with its ability to supply frequent interactions, provides pregnancy- related health knowledge to users, potentially leading to an improvement in pregnancy-related outcomes and behaviours, and, ultimately a reduction in the present economic burden related to in-person interventions. TRIAL REGISTRATION: ISRCTN, ISRCTN16254958. Registered 20 December 2019, http://www.isrctn.com/ ISRCTN16254958.

Impact of anthocyanin component and metabolite of Saskatoon berry on gut microbiome and relationship with fecal short chain fatty acids in diet-induced insulin resistant mice.

Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.

Impact of Germinated Brown Rice and Brown Rice on Metabolism, Inflammation, and Gut Microbiome in High Fat Diet-Induced Insulin Resistant Mice.

The constituents of germinated brown rice (GBR), brown rice (BRR), and white rice (WHR) and their impact on metabolism, inflammation, and gut microbiota in high fat (HF) diet-fed mice were examined. The contents of total fiber and γ-aminobutyric acid in BRR and GBR were higher than that in WHR (p < 0.05). Male C57 BL/6J mice received HF diet+26 g% of WHR, BRR, or GBR for 12 weeks. BRR and GBR comparably reduced HF diet-induced increases in fasting plasma glucose, lipids, insulin resistance, and inflammatory markers compared to WHR (p < 0.01). The abundance of fecal Bacteroidetes in mice fed HF+GBR or HF+BRR was higher than in HF+WHR-fed mice (p < 0.05). The abundance of fecal Lactobacillus gasseri in GBR-fed mice was greater than that in WHR- or BRR-fed mice (p < 0.05). The results indicated that GBR or BRR attenuated hyperglycemia, insulin resistance, and inflammation in mice. HF+GBR, but not HF+BRR, increased a probiotic bacteria in the gut.

The short-term effect of a mHealth intervention on gestational weight gain and health behaviors: The SmartMoms Canada pilot study.

Gestational weight gain (GWG) has been shown to impact several maternal-infant outcomes. Since healthcare provider guidance on weight gain and healthy behaviors alone has failed to help women to meet guidelines during pregnancy, a practical adjunctive approach is to deliver evidence-based behavior change programs through mobile interventions. The present study aimed to assess the short-term effect of the SmartMoms Canada app to promote adequate GWG and healthy behaviors. Twenty-nine pregnant women were recruited in this app-based intervention trial to test whether a higher app usage (≥ 3.8 min·week-1) between 12-20 gestational weeks and 24-28 gestational weeks improved GWG, diet, physical activity, and sleep, compared to women with a lower app usage (< 3.8 min·week-1). Two-way mixed ANOVA for repeated measures was used to estimate the effect of the app usage and time, as well as their interaction on GWG and healthy behaviors. The likelihood ratio was used to examine the association between app usage categorization and GWG classification. Cramer's V statistic was used to estimate the effect size for interpretation of the association. Pregnant women using the SmartMoms Canada app more frequently had a higher moderate-to-vigorous physical activity (MVPA) daily average when compared with women with a lower usage (mean difference: 17.84 min/day, 95% CI: 2.44; 33.25). A moderate effect size (28.6% vs. 15.4%; Cramer's V = 0.212) was found for the association between app categorization and rate of GWG, representing a greater adherence to the GWG guidelines in women in the higher app usage group vs. the lower app usage group. Considering other physical activity, diet, and sleep variables, no app categorization effect was observed. A short-term higher usage of SmartMoms Canada app has a positive effect on objectively-measured MVPA.

Effect of selenium biofortification on bioactive compounds and antioxidant activity in germinated black soybean.

Biofortification using inorganic selenium has become an effective strategy to enhance selenium content in crops. In the present study, the effects of selenium biofortification on the chemical composition and antioxidant capacity of black soybean (BS) during germination were studied. The contents of selenium, total sugar, vitamin C, γ-aminobutyric acid, total polyphenols, and total flavonoids in selenium biofortified germinated black soybeans (GBS-Se) significantly increased compared to germinated black soybeans (GBS). However, the contents of soluble protein, fat, and reducing sugar were decreased, while fatty acid composition was not significantly different between GBS and BS. HPLC analysis showed that 12 phenolic acids of all samples, which mainly existed in free forms. Their contents increased at low concentration of selenium and decreased along with the rise of selenium concentrations. The antioxidant activity of GBS-Se as analyzed by Pearson correlation analysis positively correlated with the accumulation of phenolic substances. Principal component analysis (PCA) showed that GBS and GBS-Se were significantly different from BS. Moreover, the physicochemical indexes of GBS showed regularly changes with increasing selenium content, and those of GBS-Se50 and GBS-Se75 were significantly different from GBS. The results provide a systematic evaluation on the effect of selenium fortification on the germination of seeds and useful information for the development of Se-enriched functional foods. PRACTICAL APPLICATION: The organic selenium black soybean (BS) produced by the germination method can be directly processed and eaten to improve human health. In addition, complexes of organic selenium, vitamin C, and γ-aminobutyric acid of germinated BS can be developed into functional substances and applied to food or health products as functional ingredient and/or natural antioxidant supplements.

Dose-Responses Relationship in Glucose Lowering and Gut Dysbiosis to Saskatoon Berry Powder Supplementation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice.

Administration of freeze-dried powder of Saskatoon berry (SB), a popular fruit enriched with antioxidants, reduced glucose level, inflammatory markers and gut microbiota disorder in high fat-high sucrose (HFHS) diet-induced insulin resistant mice. The present study examined the dose-response relationship in metabolic, inflammatory and gut microbiotic variables to SB power (SBp) supplementation in HFHS diet-fed mice. Male C57 BL/6J mice were fed with HFHS diet supplemented with 0, 1%, 2.5% or 5% SBp for 11 weeks. HFHS diet significantly increased the levels of fast plasma glucose (FPG), cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), tumor necrosis factor-α, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1, but decreased fecal Bacteroidetes phylum bacteria and Muribaculaceae family bacteria compared to low fat diet. SBp dose-dependently reduced metabolic and inflammatory variables and gut dysbiosis in mice compared with mice receiving HFHS diet alone. Significant attenuation of HFHS diet-induced biochemical disorders were detected in mice receiving ≥1% SBp. The abundances of Muribaculaceae family bacteria negatively correlated with body weights, FPG, lipids, insulin, HOMA-IR and inflammatory markers in the mice. The results suggest that SBp supplementation dose-dependently attenuated HFHS diet-induced metabolic and inflammatory disorders, which was associated with the amelioration of gut dysbiosis in the mice.

Saskatoon berry powder reduces hepatic steatosis and insulin resistance in high fat-high sucrose diet-induced obese mice.

Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.

Impact of remote prenatal education on program participation and breastfeeding of women in rural and remote Indigenous communities.

BACKGROUND: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities. METHODS: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017. FINDINGS: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p < 0·001). Availability of high-speed Wi-Fi and/or postpartum supporting team were associated with favorite study outcomes. Positive feedback on the remote prenatal education was received from participants. INTERPRETATION: The findings suggest that remote prenatal education is feasible and effective for improving the breastfeeding rate and engaging pregnant women to participate in the prenatal program in rural or remote FN communities. The remote prenatal education remained active during COVID-19 in the participating communities, which suggests an advantage to expand remote prenatal education in other Indigenous communities. FUNDING: Canadian Institutes of Health Research, the Lawson Foundation and University of Manitoba.

Intrauterine exposure to diabetes and risk of cardiovascular disease in adolescence and early adulthood: a population-based birth cohort study.

BACKGROUND: It is unclear whether intrauterine exposure to maternal diabetes is associated with risk factors for cardiovascular disease and related end points in adulthood. We examined this potential association in a population-based birth cohort followed up to age 35 years. METHODS: We performed a cohort study of offspring born between 1979 and 2005 (n = 293 546) and followed until March 2015 in Manitoba, Canada, using registry-based administrative data. The primary exposures were intrauterine exposure to gestational diabetes and type 2 diabetes mellitus. The primary outcome was a composite measure of incident cardiovascular disease events, and the secondary outcome was a composite of risk factors for cardiovascular disease in offspring followed up to age 35 years. RESULTS: The cohort provided 3 628 576 person-years of data (mean age at latest follow-up 20.5 [standard deviation 6.4] years, 49.3% female); 2765 (0.9%) of the offspring experienced a cardiovascular disease end point, and 12 673 (4.3%) experienced a cardiovascular disease risk factor. After propensity score matching, the hazard for cardiovascular disease end points was elevated in offspring exposed to gestational diabetes (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12-1.79) but not type 2 diabetes (adjusted HR 1.40, 95% CI 0.98-2.01). A similar association was observed for cardiovascular disease risk factors (gestational diabetes: adjusted HR 1.92, 95% CI 1.75-2.11; type 2 diabetes: adjusted HR 3.40, 95% CI 3.00-3.85). INTERPRETATION: Intrauterine exposure to maternal diabetes was associated with higher morbidity and risk related to cardiovascular disease among offspring up to 35 years of age.

Impact of Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice.

The present study assessed the effects of freeze-dried cyanidin-3-glucoside (C3G), an anthocyanin enriched in dark-red berries, compared to Saskatoon berry powder (SBp) on metabolism, inflammatory markers and gut microbiota in high fat-high sucrose (HFHS) diet-induced insulin-resistant mice. Male C57 BL/6J mice received control, HFHS, HFHS + SBp (8.0 g/kg/day) or HFHS + C3G (7.2 mg/kg/day, equivalent C3G in SBp) diet for 11 weeks. The HFHS diet significantly increased plasma levels of glucose, cholesterol, triglycerides, insulin resistance and inflammatory markers. The HFHS + SBp diet increased the Bacteroidetes/Firmicutes (B/F) ratio and relative abundance of Muriculaceae family bacteria in mouse feces detected using 16S rRNA gene sequencing. The HFHS + SBp or HFHS + C3G diet attenuated glucose, lipids, insulin resistance and inflammatory markers, and increased the B/F ratio and Muriculaceae relative abundance compared to the HFHS diet alone. The relative abundances of Muriculaceae negatively correlated with body weight, glucose, lipids, insulin resistance and inflammatory mediators. Functional predication analysis suggested that the HFHS diet upregulated gut bacteria genes involved in inflammation, and downregulated bacteria involved in metabolism. C3G and SBp partially neutralized HFHS diet-induced alterations of gut bacteria. The results suggest that C3G is a potential prebiotic, mitigating HFHS diet-induced disorders in metabolism, inflammation and gut dysbiosis, and that C3G contributes to the metabolic beneficial effects of SBp.

Assessment of binding interaction dihydromyricetin and myricetin with bovine lactoferrin and effects on antioxidant activity.

The binding interactions of bovine lactoferrin (BLF) with two flavonoids dihydromyricetin (DMY) and myricetin (MY) were investigated by the multi-spectroscopic, microscale thermophoresis (MST) techniques, molecular docking, and then their antioxidant activities were studied by detection of free radical scavenging activity against DPPH. Results of UV-vis and fluorescence spectroscopies showed that DMY/MY and BLF formed the ground state complex through the static quenching mechanism. Moreover, MY with more planar stereochemical structure had higher affinity for BLF than DMY with twisted stereochemical structure, according to the binding constant (Kb), free energy change (ΔG°), dissociation constant (Kd) and donor-acceptor distance (r). Thermodynamic parameters revealed that hydrogen bond and van der Waals force were major forces in the formation of BLF-DMY complex, while hydrophobic interactions played major roles in the formation of BLF-DMY complex. The circular dichroism (CD) study indicated that MY induced more conformational change in BLF than DMY. Furthermore, molecular modeling provided insights into the difference of binding interactions between BLF and two flavonoids. Finally, the radical scavenging activity assays indicated the presence of BLF delayed the decrease in antioxidant capacities of two flavonoids. These results were helpful to understand the binding mechanism and biological effects of non-covalent BLF-flavonoid interaction.

North American Wild Rice-Attenuated Hyperglycemia in High-Fat-Induced Obese Mice: Involvement of AMP-Activated Protein Kinase.

Previous studies indicated that North American wild rice (WIR) reduced atherosclerosis and vascular inflammation in low-density lipoprotein receptor knockout mice. The effects of WIR on hyperglycemia in diabetic animal models have not been documented. The present study aims to determine the impact of WIR on glucose metabolism in high-fat (HF)-induced diabetic mice and a key modulator. Male C57 BL/J6 mice were treated with a control diet and a HF diet supplemented with 26% (weight/weight, a substitute for carbohydrates in the diet) of WIR or white rice (WHR) (n = 8/group) for 11 weeks. HF + WHR diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin, insulin resistance, monocyte adhesion, and the levels of relevant inflammatory mediators (tumor necrotic factor-α, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1) in mice compared to the control diet (p < 0.01). HF + WIR significantly reduced HF diet-induced metabolic and inflammatory changes compared to the HF + WHR diet (p < 0.01). Metabolomics analysis indicated that an array of metabolites related to glucose metabolism was significantly more abundant in WIR than in WHR, including adenosine 5'-monophosphate (AMP), a potent agonist for AMP-activated protein kinase or AMPK. WIR normalized HF diet-induced reduction in the abundance of phospho-AMPKα in skeletal muscle, liver, and adipose tissue from the mice. The findings for the first time demonstrated that WIR decreased HF diet-induced hyperglycemia in mice compared to WHR. The metabolic benefits of WIR may result, at least in part, from the activation of AMPKα in insulin-sensitive tissue in the mice.

Bioactive Components and Health Benefits of Saskatoon Berry.

In response to the recent rise in numbers of diabetes patients, many treatments have been developed; but currently, oral antihyperglycemic agents and insulin are still the main clinical treatments. Since current drugs have limitations and harmful side effects, research in alternative treatments has been sought. This article reviews recent research updates of Saskatoon berries (SB), covering its background information, its main active ingredients, its structure, and its function. Flavonoid compounds in Saskatoon berries, in particular flavanol, anthocyanin, and proanthocyanin, possess anti-inflammatory, antitumor, and antidiabetes impacts. The current review synthesizes the latest research on the health benefits of Saskatoon berry in a variety of domains. With further research, SB has the potential to help treat and prevent diabetes in the future.

Mitochondrial Respiration Correlates with Prognostic Markers in Chronic Lymphocytic Leukemia and Is Normalized by Ibrutinib Treatment.

Mitochondrial bioenergetics profiling, a measure of oxygen consumption rates, correlates with prognostic markers and can be used to assess response to therapy in chronic lymphocytic leukemia (CLL) cells. In this study, we measured mitochondrial respiration rates in primary CLL cells using respirometry to evaluate mitochondrial function. We found significant increases in mitochondrial respiration rates in CLL versus control B lymphocytes. We also observed amongst CLL patients that advanced age, female sex, zeta-chain-associated protein of 70 kD (ZAP-70+), cluster of differentiation 38 (CD38+), and elevated ß2-microglobulin (ß2-M) predicted increased maximal respiration rates. ZAP-70+ CLL cells exhibited significantly higher bioenergetics than B lymphocytes or ZAP-70- CLL cells and were more sensitive to the uncoupler, carbonyl cyanide-p-trifluoro-methoxyphenylhydrazone (FCCP). Univariable and multivariable linear regression analysis demonstrated that ZAP-70+ predicted increased maximal respiration. ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton's tyrosine kinase (BTK) inhibitor. Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL. Our data support evaluation of mitochondrial respiration as a preclinical tool for the response assessment of CLL cells.

Impact of Saskatoon berry powder on insulin resistance and relationship with intestinal microbiota in high fat-high sucrose diet-induced obese mice.

The present study examined the impact of Saskatoon berry powder (SBp) on insulin resistance, inflammation and intestinal microbiota in diet-induced obese mice. Male C57 BL/6 J mice were fed control diet, high fat-high sucrose (HFHS) diet or HFHS+5% SBp (HFHS+B) diet for 15 weeks. The composition of fecal bacterial community was characterized using the Illumina sequencing of V4 region of 16S rRNA gene. HFHS diet increased body weight, fasting plasma glucose, cholesterol, triglycerides, insulin, homeostatic model assessment-insulin resistance, monocyte adhesion, tumor necrosis factor-α, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, intracellular cell adhesion molecule-1, urokinase plasminogen activator and its receptor in plasma or aortae compared to the control diet. HFHS+B diet postponed the increase in body weight, suppressed HFHS diet-induced disorders in the metabolic and inflammatory variables. The ratio of Firmicutes/Bacteroidetes in the HFHS group was higher than that in the control group (P<.01), and that in the HFHS+B group was lower than that in the HFHS group (P<.05). The abundances of S24-7 family negatively correlated with body weight and tested metabolic or inflammatory variables. The results suggest that SBp attenuated HFHS diet-induced metabolic disorders and vascular inflammation in gut microbiota in mice.

Association of Gestational Diabetes and Type 2 Diabetes Exposure In Utero With the Development of Type 2 Diabetes in First Nations and Non-First Nations Offspring.

Importance: Type 2 diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 diabetes is important to address the intergenerational burden of illness. Objective: To investigate the association of in utero exposure to gestational diabetes and type 2 diabetes, stratified by FN status, with the development of type 2 diabetes in offspring. Design, Setting, and Participants: This cohort study was derived from the linkage of a pediatric diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 diabetes, monogenic diabetes, or secondary diabetes were excluded. Exposures: Primary exposures included maternal gestational diabetes or type 2 diabetes and FN status. Main Outcomes and Measures: The primary outcome was incident type 2 diabetes in offspring by age 30 years. Results: In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and diabetes exposure were associated with incident type 2 diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 diabetes exposure conferred a greater risk to offspring compared with gestational diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P < .001). Compared with no diabetes exposure, any diabetes exposure accelerated the time to the development of type 2 diabetes in offspring by a factor of 0.74 (95% CI, 0.62-0.90) for gestational diabetes and a factor of 0.50 (95% CI, 0.45-0.57) for type 2 diabetes. First Nations offspring had a higher risk compared with non-FN offspring (0.96 vs 0.14 cases per 1000 person-years, P < .001). First Nations offspring had accelerated type 2 diabetes onset by a factor of 0.52 (95% CI, 0.49-0.55) compared with non-FN offspring. Neither interaction between FN and type 2 diabetes (0.92; 95% CI, 0.80-1.05) nor interaction between FN and gestational diabetes (0.97; 95% CI, 0.77-1.20) was significant (P = .21 and P = .75, respectively). Conclusions and Relevance: Important differences exist in offspring risk based on type of diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.

Germinated Brown Rice Attenuates Atherosclerosis and Vascular Inflammation in Low-Density Lipoprotein Receptor-Knockout Mice.

The present study investigates the impact of germinated brown rice (GBR) on atherosclerosis and the underlying mechanism in low-density lipoprotein receptor-knockout (LDLr-KO) mice. The intensity of atherosclerosis in aortas of LDLr-KO mice receiving diet supplemented with 60% GBR (weight/weight) was significantly less than that in mice fed with 60% white rice (WR) or control diet ( p < 0.05); all diets contained 0.06% cholesterol. WR or GBR diet did not significantly alter plasma total or LDL-cholesterol, fecal sterols, or glucose, or the activities of antioxidant enzymes, compared to the control diet. The adhesion of monocytes to aortas from LDLr-KO mice fed with WR diet was significantly more than that from mice receiving the control diet ( p < 0.01). GBR diet decreased monocyte adhesion to aortas compared to WR diet ( p < 0.01). GBR diet also reduced the levels of plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) in plasma, and the abundances of MCP-1, PAI-1, TNF-α, intracellular cell adhesion molecule-1, toll-like receptor-4, PAI-1, LDLr-like protein, and urokinase plasminogen activator and its receptor in aortas or hearts from LDLr-KO mice in comparison to the WR diet ( p < 0.05, 0.01, respectively). The findings suggest that GBR administration attenuated atherosclerosis and vascular inflammation in LDLr-KO mice compared to WR. The anti-atherosclerotic effect of GBR in LDLr-KO mice at least in part results from its anti-inflammatory activity.