A Quinoa Protein Hydrolysate Fractionated by Electrodialysis with Ultrafiltration Membranes Improves Maternal and Fetal Outcomes in a Mouse Model of Gestational Diabetes Mellitus.

SCOPE: Quinoa intake exerts hypoglycemic and hypolipidemic effects in animals and humans. Although peptides from quinoa inhibit key enzymes involved in glucose homeostasis in vitro, their in vivo antidiabetic properties have not been investigated. METHODS AND RESULTS: This study evaluated the effect of oral administration of a quinoa protein hydrolysate (QH) produced through enzymatic hydrolysis and fractionation by electrodialysis with ultrafiltration membrane (EDUF) (FQH) on the metabolic and pregnancy outcomes of Lepdb/+ pregnant mice, a preclinical model of gestational diabetes mellitus. The 4-week pregestational consumption of 2.5 mg mL-1 of QH in water prevented glucose intolerance and improves hepatic insulin signaling in dams, also reducing fetal weights. Sequencing and bioinformatic analyses of the defatted FQH (FQHD) identified 11 peptides 6-10 amino acids long that aligned with the quinoa proteome and exhibited putative anti-dipeptidyl peptidase-4 (DPP-IV) activity, confirmed in vitro in QH, FQH, and FDQH fractions. Peptides homologous to mouse and human proteins enriched for biological processes related to glucose metabolism are also identified. CONCLUSION: Processing of quinoa protein may be used to develop a safe and effective nutritional intervention to control glucose intolerance during pregnancy. Further studies are required to confirm if this nutritional intervention is applicable to pregnant women.

Probiotic Supplementation, Hepatic Fibrosis, and the Microbiota Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment. OBJECTIVES: To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients. METHODS: In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE. RESULTS: The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment. CONCLUSIONS: Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047.

Dietary citrate acutely induces insulin resistance and markers of liver inflammation in mice.

Citrate is widely used as a food additive being part of virtually all processed foods. Although considered inert by most of the regulatory agencies in the world, plasma citrate has been proposed to play immunometabolic functions in multiple tissues through altering a plethora of cellular pathways. Here, we used a short-term alimentary intervention (24 hours) with standard chow supplemented with citrate in amount corresponding to that found in processed foods to evaluate its effects on glucose homeostasis and liver physiology in C57BL/6J mice. Animals supplemented with dietary citrate showed glucose intolerance and insulin resistance as revealed by glucose and insulin tolerance tests. Moreover, animals supplemented with citrate in their food displayed fed and fasted hyperinsulinemia and enhanced insulin secretion during an oral glucose tolerance test. Citrate treatment also amplified glucose-induced insulin secretion in vitro in INS1-E cells. Citrate supplemented animals had increased liver PKCα activity and altered phosphorylation at serine or threonine residues of components of insulin signaling including IRS-1, Akt, GSK-3 and FoxO1. Furthermore, citrate supplementation enhanced the hepatic expression of lipogenic genes suggesting increased de novo lipogenesis, a finding that was reproduced after citrate treatment of hepatic FAO cells. Finally, liver inflammation markers were higher in citrate supplemented animals. Overall, the results demonstrate that dietary citrate supplementation in mice causes hyperinsulinemia and insulin resistance both in vivo and in vitro, and therefore call for a note of caution on the use of citrate as a food additive given its potential role in metabolic dysregulation.

Purple grumixama anthocyanins (Eugenia brasiliensis Lam.) attenuate obesity and insulin resistance in high-fat diet mice.

Some polyphenols have been reported to modulate the expression of several genes related to lipid metabolism and insulin signaling, ameliorating metabolic disorders. We investigated the potential for the polyphenols of two varieties of grumixama, the purple fruit rich in anthocyanins and the yellow fruit, both also rich in ellagitannins, to attenuate obesity-associated metabolic disorders. Mice were fed a high fat and high sucrose diet, supplemented daily with yellow and purple extracts (200 mg per kg of body weight) for eight weeks. Purple grumixama supplementation was found to decrease body weight gain, improve insulin sensitivity and glucose-induced hyperinsulinemia, and reduce hepatic triglyceride accumulation. A decrease in intrahepatic lipids in mice treated with the purple grumixama extract was associated with lipid metabolism modulation by the PPAR signaling pathway. LPL, ApoE, and LDLr were found to be down-regulated, while Acox1 and ApoB were found to be upregulated. Some of these genes were also modulated by the yellow extract. In addition, both extracts decreased oGTT and plasma LPS. The results were associated with the presence of phenolic acids and urolithins. In conclusion, most likely the anthocyanins from the purple grumixama phenolic extract is responsible for reducing obesity and insulin resistance.

Two polyphenol-rich Brazilian fruit extracts protect from diet-induced obesity and hepatic steatosis in mice.

Consumption of polyphenol-rich food is associated with better metabolic health. Tucum-do-Pantanal (Bactris setosa Mart) and taruma-do-cerrado (Vitex cymosa Bertero ex Spreng) are underexploited native Brazilian fruits with an important source of phytochemicals. In this study, we assessed the effects of 100 mg kg-1 tucum (TPE) and taruma (TCE) extracts on diet-induced obesity (DIO) C57BL/6J mice. After 8 weeks of daily treatment, TPE and TCE were found to significantly prevented the diet-induced body weight gain and fully protected against hepatic steatosis associated with a tendency to stimulate hepatic AMPK phosphorylation. TPE reduced visceral obesity and improved glucose metabolism as revealed by an improvement of the insulin tolerance test, a reduction in the insulin fasting level, and a decreased glucose-induced hyperinsulinemia during an oral glucose tolerance test. TPE and TCE showed promising effects on the treatment of obesity and NAFLD, furthermore, TPE on insulin resistance.

Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPARγ-dependent and PPARγ-independent actions.

SCOPE: We tested herein the hypothesis that peroxisome proliferator activated receptor γ (PPARγ) is a major mediator of omega-3 (n-3) protective actions against high-fat diet (HFD) induced obesity, glucose intolerance, and adipose tissue inflammation. METHODS AND RESULTS: C57BL6 wild-type and fat-1 transgenic (fat-1) mice were fed a low-fat diet (LFD) or HFD, treated or not with PPARγ antagonist, and evaluated for energy balance, adiposity, glucose tolerance, and adipose tissue inflammation. Fat-1 mice were protected from obesity, fasting hyperglycemia, glucose intolerance, and adipose tissue inflammation. PPARγ inhibition completely abolished fat-1 protection against HFD-induced glucose intolerance, but not obesity or adipose tissue inflammation. To investigate the role of myeloid cell as mediator of n-3 beneficial metabolic actions, mice with deletion (LyzM-PPARγ(KO)) or nondeletion (LyzM-PPARγ(WT)) of PPARγ in myeloid cells were fed either LFD or HFD (lard) or an HFD rich in n-3 (fish oil). Our findings indicate that myeloid cell associated PPARγ is not involved in the attenuation of HFD-induced glucose intolerance and adipose tissue inflammation induced by n-3. CONCLUSION: High endogenous n-3 fatty acid levels protect from HFD obesity, glucose intolerance, and adipose tissue inflammation. Among these, only protection against glucose intolerance is mediated by non-myeloid cell PPARγ.