Protocol for a pilot study: Feasibility of a web-based platform to improve nutrition, mindfulness, and physical function in people living with Post COVID-19 condition (BLEND).

Individuals with Post COVID-19 condition (PCC), or long COVID, experience symptoms such as fatigue, muscle weakness, and psychological distress, including anxiety, depression, or sleep disorders that persist after recovery from COVID-19. These ongoing symptoms significantly compromise quality of life and diminish functional capacity and independence. Multimodal digital interventions targeting behavioural factors such as nutrition and mindfulness have shown promise in improving health outcomes of people with chronic health conditions and may be beneficial for those with PCC. The BLEND study (weB-based pLatform to improve nutrition, mindfulnEss, and physical function, in patients with loNg COVID) study is an 8-week pilot randomized controlled trial evaluating the feasibility of a digital wellness platform compared to usual care among individuals with PCC. The web-based wellness platform employed in this study, My Viva Plan (MVP)®, integrates a holistic, multicomponent approach to promote wellness. The intervention group receives access to the digital health platform for 8 weeks with encouragement for frequent interactions to improve dietary intake and mindfulness. The control group receives general content focusing on improvements in dietary intake and mindfulness. Assessments are conducted at baseline and week 8. The primary outcome is the feasibility of platform use. Secondary and exploratory outcomes include a between-group comparison of changes in body composition, nutritional status, quality of life, mindfulness, physical activity, and physical performance after 8 weeks. Findings of this study will inform the development of effective web-based wellness programs tailored for individuals with PCC to promote sustainable behavioural changes and improved health outcomes.

Low-fat cheese ameliorates glucose intolerance and normalizes insulin secretion in a rat model of type 2 diabetes by promoting ß-cell recovery.

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10 min (p < 0.05) but the iAUC was highly variable in all groups and statistical differences were not detected (p > 0.05). ß-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF (p < 0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced ß-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks.

Dairy product consumption and risk of non-alcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: It is unclear whether regular consumption of dairy products is associated with the risk of developing non-alcoholic fatty liver disease (NAFLD). Thus, we conducted a systematic review followed by a meta-analysis of studies reporting on the association of dairy consumption with NAFLD risk. METHODS AND RESULTS: We comprehensively searched PubMed, Web of Science, and Scopus for observational studies that evaluated the association between dairy intake and NAFLD likelihood that were published before September 1, 2022. The reported odds ratios (ORs) of fully adjusted models and their 95% confidence intervals (CIs) were pooled using a random-effects model for the meta-analysis. Out of 1206 articles retrieved, 11 observational studies, including 43,649 participants and 11,020 cases, were included. Pooled OR indicated a significant association between dairy intake and NAFLD (OR = 0.90; 95% CI: 0.83, 0.98; I2 = 67.8%, n = 11). Pooled ORs revealed that milk (OR: 0.86; 95% CI: 0.78, 0.95; I2 = 65.7%, n = 6), yogurt (OR: 0.88; 95% CI: 0.82; I2 = 0.0%, n = 4), and high-fat dairy (OR: 0.38; 95% CI: 0.19, 0.75; I2 = 0.0%, n = 5) consumption was inversely associated with NAFLD while cheese was not linked to NAFLD risk. CONCLUSION: We observed that consumption of dairy products is linked to a reduced risk of developing NAFLD. Overall, the data in the source articles is of low to moderate quality; therefore, further observational studies are required to support the current findings (PROSPERO Reg. number: CRD42022319028).

Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.

Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.

Association of dairy consumption patterns with the incidence of type 2 diabetes: Findings from Alberta's Tomorrow Project.

BACKGROUND AND AIMS: We aimed to extract dairy consumption patterns of men and women from a population-based cohort and then assess the association of each consumption pattern with incident T2D risk. METHODS AND RESULTS: This prospective study was conducted within the framework of Alberta's Tomorrow Project (ATP), in which 8615 men and 15,016 women provided information on dietary intake by completing a food-frequency questionnaire at baseline, and then were followed up over time to determine the incidence of T2D via questionnaires. Principal Component Analysis (PCA) was used to extract dairy consumption patterns (DCPs). The association between each extracted pattern and T2D incidence was estimated using multivariable logistic regression models.The incidence of T2D among men and women was 3.8 and 3.2%, respectively, and the mean duration of follow-up was 5.2 years. Three major DCPs were identified. After controlling for potential confounders, the OR for risk of T2D in men in the highest compared with those in the lowest quartile of the DCP3 (whole milk, regular cheese, and non-fat milk as a beverage and in cereal) was 0.64 (95%CI: 0.47 to 0.88, P-trend=0.001), whereas it was not significant for women. DCP1 and DCP2 were not associated with incident T2D in men or women. CONCLUSION: Adherence to a DCP characterized by higher consumption of whole milk, regular cheese, and non-fat milk was associated with decreased risk of incident T2D only in men. Our results support current evidence that a combination of different dairy products, regardless of their fat content, might be favorable for health maintenance, at least in men.

Elevated miR-143 and miR-34a gene expression in human visceral adipose tissue are associated with insulin resistance in non-diabetic adults: a cross-sectional study.

OBJECTIVE: We aimed to evaluate the association of miR-143 and miR-34a expression in human visceral (VAT) and subcutaneous (SAT) adipose tissues with insulin resistance (IR). METHODS: VAT and SAT were obtained from 176 participants without diabetes. miR-143 and miR-34a expressions in VAT and SAT were measured using qRT-PCR. Fasting serum insulin and glucose concentration, homeostatic model assessment of IR index (HOMA-IR) and ß-cell function (HOMA-B), and quantitative insulin-sensitivity check index (QUICKI) were calculated. RESULTS: After adjustment for age, sex and body mass index (BMI), VAT miR-143 expression was positively associated with fasting plasma glucose (FPG), insulin, and HOMA-IR, and negatively associated with HOMA-B and QUICKI. miR-34a expression in VAT was directly associated with FPG, insulin, and HOMA-IR and negatively associated with QUICKI. In SAT, miR-34a expression was positively associated with insulin and negatively associated with QUICKI. The interaction terms of HOMA-IR and BMI categories were significant for both miR gene expressions in VAT. After stratifying participants based on BMI, the association of miR-143 and miR-34a expressions in VAT with IR indices remained significant only in obese patients. CONCLUSION: miR-143 and miR-34a expressions in VAT were independent predictors of IR in people without diabetes, and that this association was conditional on the degree of obesity. LEVEL OF EVIDENCE: Level of evidence III, cross-sectional analytic study.

Transient antibiotic-induced changes in the neonatal swine intestinal microbiota impact islet expression profiles reducing subsequent function.

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin [30 mg/kg body wt/day; n = 7, antibiotic (ANTI)] or placebo [vehicle control; n = 7, control (CON)] from postnatal day (PND)0-13 were euthanized at PND7, 14, and 49. The metabolic phenotype along with functional, immunohistological, and transcriptional phenotypes of the pancreatic islets were studied. The gut microbiome was characterized by 16S rRNA gene sequencing, and microbial metabolites and microbiome-sensitive host molecules were measured. Compared with CON, ANTI PND7 piglets had elevated transcripts of genes involved in glucagon-like peptide 1 ((GLP-1) synthesis or signaling in islets (P < 0.05) coinciding with higher plasma GLP-1 (P = 0.11), along with increased tumor necrosis factor α (Tnf) (P < 0.05) and protegrin 1 (Npg1) (P < 0.05). Antibiotic-induced relative increases in Escherichia, Coprococcus, Ruminococcus, Dehalobacterium, and Oscillospira of the ileal microbiome at PND7 normalized after antibiotic withdrawal. In ANTI islets at PND14, the expression of key regulators pancreatic and duodenal homeobox 1 (Pdx1), insulin-like growth factor-2 (Igf2), and transcription factor 7-like 2 (Tcf7l2) was downregulated, preceding a 40% reduction of ß-cell area (P < 0.01) and islet insulin content at PND49 (P < 0.05). At PND49, a twofold elevated plasma insulin concentration (P = 0.07) was observed in ANTI compared with CON. We conclude that antibiotic treatment of neonatal piglets elicited gut microbial changes accompanied by phasic alterations in key regulatory genes in pancreatic islets at PND7 and 14. By PND49, reduced ß-cell area and islet insulin content were accompanied by elevated nonfasted insulin despite normoglycemia, indicative of islet stress.

The association of dietary and plasma fatty acid composition with FTO gene expression in human visceral and subcutaneous adipose tissues.

PURPOSE: The human obesity susceptibility gene, FTO, associates with body mass and obesity in humans through regulation of energy expenditure and intake. We aimed to determine how fatty acids in plasma and in diet associate with FTO gene expression in subcutaneous and visceral adipose tissues. METHODS: In this study, 97 participants aged ≥ 18 years were selected from patients admitted to the hospital for abdominal surgeries. Habitual dietary intake of participants was collected using a valid and reliable food frequency questionnaire (FFQ), from which the intake of fatty acids was quantified. Plasma fatty acids were assessed by gas-liquid chromatography. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues obtained by biopsy was measured by Real-Time Quantitative Reverse Transcription PCR. Standardized ß-coefficients were calculated by multivariable linear regression. RESULTS: After adjusting for age, homeostasis model insulin resistance index (HOMA-IR), and body mass index, total fatty acid intake was significantly associated with FTO gene expression in visceral (STZß = 0.208, P = 0.037) and subcutaneous (STZß = 0.236, P = 0.020) adipose tissues. Dietary intake of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) had positive significant associations with the expression of FTO in visceral (STZß = 0.227, P = 0.023; STZß = 0.346, P < 0.001, respectively) and subcutaneous (STZß = 0.227, P = 0.026; STZß = 0.274, P = 0.006, respectively) adipose tissues. There were no associations between plasma fatty acids and FTO mRNA expression in either subcutaneous or visceral adipose tissues. CONCLUSION: The weak association of dietary total fatty acids, MUFA, and PUFA with FTO gene expression in both adipose tissues may highlight the importance of dietary fatty acids composition along with total fat intake in relation to FTO gene expression.

Changes in dairy product consumption and subsequent type 2 diabetes among individuals with prediabetes: Tehran Lipid and Glucose Study.

BACKGROUND: People with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes. METHOD: This cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years. RESULTS: After almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively. CONCLUSION: In individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients.

Metformin Preserves ß-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats.

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic ß-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and ß-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on ß-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human ß-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on ß-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited ß-cell glucose-stimulated insulin secretion in vitro, stimulation of ß-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, ß-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress ß-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on ß-cell function or cell mass and, instead, early metformin treatment may help protect ß-cells from exhaustion and decompensation.

Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity.

Epicatechin (EC) is a monomeric flavan-3-ol. We have previously demonstrated that glucose-intolerant rats fed flavan-3-ols exhibit improved pancreatic islet function corresponding with an increase in circulating EC-derived metabolites. Thus, we speculate that EC may act as a cellular signaling molecule in vivo to modulate insulin secretion. In this study we further examined the effects of different concentrations of EC on H2O2 or hyperglycemia-induced ROS production, as well as on saturated fatty acid (SFA)-impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cell line in vitro. We showed that EC at a high concentration (30 µmol/L), but not a low concentration (0.3 µmol/L), significantly decreased H2O2 or hyperglycemia-induced ROS production in INS-1 cells. However, EC (0.3 µmol/L) significantly enhanced SFA-impaired GSIS in INS-1 cells. Addition of KN-93, a CaMKII inhibitor, blocked the effect of EC on insulin secretion and decreased CaMKII phosphorylation. Addition of GW1100, a GPR40 antagonist, significantly attenuated EC-enhanced GSIS, but only marginally affected CaMKII phosphorylation. These results demonstrate that EC at a physiological concentration promotes GSIS in SFA-impaired ß-cells via activation of the CaMKII pathway and is consistent with its function as a GPR40 ligand. The findings support a role for EC as a cellular signaling molecule in vivo and further delineate the signaling pathways of EC in ß-cells.

IKKß inhibition prevents fat-induced beta cell dysfunction in vitro and in vivo in rodents.

AIMS/HYPOTHESIS: We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase ß (IKKß), which is activated by oxidative stress, is also implicated. METHODS: Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKß inhibitor salicylate. Thereafter, beta cell function was evaluated in vivo using hyperglycaemic clamps or ex vivo in islets isolated from fat-treated rats. We also exposed rat islets to oleate in culture, with or without salicylate and 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; BMS-345541 (BMS, another inhibitor of IKKß) and evaluated beta cell function in vitro. Furthermore, oleate was infused in mice treated with BMS and in beta cell-specific Ikkb-null mice. RESULTS: 48 h infusion of fat impaired beta-cell function in vivo, assessed using the disposition index (DI), in rats (saline: 1.41 ± 0.13; oleate: 0.95 ± 0.11; olive oil [OLO]: 0.87 ± 0.15; p < 0.01 for both fats vs saline) and in mice (saline: 2.51 ± 0.39; oleate: 1.20 ± 0.19; p < 0.01 vs saline) and ex vivo (i.e., insulin secretion, units are pmol insulin islet-1 h-1) in rat islets (saline: 1.51 ± 0.13; oleate: 1.03 ± 0.10; OLO: 0.91 ± 0.13; p < 0.001 for both fats vs saline) and the dysfunction was prevented by co-infusion of salicylate in rats (oleate + salicylate: 1.30 ± 0.09; OLO + salicylate: 1.33 ± 0.23) or BMS in mice (oleate + BMS: 2.25 ± 0.42) in vivo and by salicylate in rat islets ex vivo (oleate + salicylate: 1.74 ± 0.31; OLO + salicylate: 1.54 ± 0.29). In cultured islets, 48 h exposure to oleate impaired beta-cell function ([in pmol insulin islet-1 h-1] control: 0.66 ± 0.12; oleate: 0.23 ± 0.03; p < 0.01 vs saline), an effect prevented by both inhibitors (oleate + salicylate: 0.98 ± 0.08; oleate + BMS: 0.50 ± 0.02). Genetic inhibition of IKKß also prevented fat-induced beta-cell dysfunction ex vivo ([in pmol insulin islet-1 h-1] control saline: 0.16 ± 0.02; control oleate: 0.10 ± 0.02; knockout oleate: 0.17 ± 0.04; p < 0.05 control saline vs. control oleate) and in vivo (DI: control saline: 3.86 ± 0.40; control oleate: 1.95 ± 0.29; knockout oleate: 2.96 ± 0.24; p < 0.01 control saline vs control oleate). CONCLUSIONS/INTERPRETATION: Our results demonstrate a causal role for IKKß in fat-induced beta cell dysfunction in vitro, ex vivo and in vivo.

Isoferulic acid prevents methylglyoxal-induced protein glycation and DNA damage by free radical scavenging activity.

BACKGROUND: Isoferulic acid (IFA), a naturally occurring cinnamic acid derivative, is a main active ingredient of the rhizoma of Cimicifuga dahurica. It has been shown various pharmacological activities. The aim of the study was to investigate the effect of IFA against MG-induced protein glycation and oxidative DNA damage. Free radical scavenging activity and the MGO-trapping abilities of IFA were also investigated. METHODS: The fluorescent MG-derived AGEs and non-fluorescent N(ε)-(carboxymethyl) lysine (N(ε)-CML) was measured using a spectrofluorometer and an enzyme linked immunosorbant assay (ELISA). Protein carbonyl content was used to detect protein oxidation. Gel electrophoresis was used to determine DNA damage. Superoxide anion radicals and hydroxyl radicals were determined using cytochrome c reduction assay and thiobarbituric acid reactive 2-deoxy-D-ribose oxidation products, respectively. The MG-trapping capacity was performed by HPLC. RESULTS: IFA (1.25-5 mM) inhibited the formation of fluorescent MG-derived AGEs, and N(ε)-CML, and protein carbonyl in bovine serum albumin. In addition, IFA (0.1-1 mM) also prevented MG/lysine-mediated oxidative DNA damage in the presence and absence of copper ion. The protective ability of IFA was directly correlated to inhibition of hydroxyl and superoxide anion radical generation during the reaction of MG and lysine. Most notably, IFA had no the directly trapping ability to MG. CONCLUSIONS: The present results highlighted that free radical scavenging activity, but not the MG-trapping ability, is the mechanism of IFA for preventing MG-induced protein glycation and DNA damage.

Characterizing severe obesity in children and youth referred for weight management.

BACKGROUND: Severe obesity (SO) in pediatrics has become increasing prevalent in recent decades.The objective of our study was to examine differences in demographic, anthropometric, cardiometabolic, and lifestyle variables in children and youth with SO versus their less overweight/obese (OW/OB) peers. METHODS: A retrospective medical record review of 6-19 year old participants enrolled in an outpatient pediatric weight management clinic was conducted. SO (body mass index [BMI] ≥99(th) percentile) and OW/OB (BMI ≥85(th) and <99(th) percentile) groups were created according to Centers for Disease Control and Prevention definitions. Demographic, anthropometric, cardiometabolic and lifestyle data reported at baseline (pre-intervention) were retrieved. RESULTS: Of the 345 participants, most were girls (56.2%), Caucasian (78.7%), and had family incomes > $50,000/year (65.7%). The SO group (n = 161) had lower HDL-cholesterol and higher liver enzymes, insulin resistance and blood pressure than the OW/OB group (n = 184; all p < 0.01). They also reported higher total energy intakes, fewer steps/day, less moderate-to-vigorous physical activity, and more leisure time screen time (all p < 0.02) than their leaner peers. Compared to the OW/OB group, a higher proportion of individuals in the SO group possessed cardiometabolic risk factors, including high triglycerides (45.8% vs 58.5%), alanine aminotransferase (55.4% vs 81.4%), insulin resistance (55.6% vs 82.1%), systolic blood pressure (11.5% vs 27.3%), diastolic blood pressure (17.8% vs 30.0%), and low HDL-cholesterol (44.6% vs 64.6%; all p < 0.02). Aside from the ~75% of participants (groups combined) who met the daily recommended intakes of grain and meat products, <50% of boys and girls met any of the remaining nutrition and physical activity-related recommendations. Compared to the OW/OB group, greater proportions of children and youth in the SO group failed to meet moderate-to-vigorous physical activity (48.4% vs 31.9%) and leisure-time-screen-time recommendations (43.4% vs 28.3%; both p < 0.05). CONCLUSION: Children and youth with SO have a worse cardiometabolic profile and less favorable lifestyle habits than their OW/OB peers. These differences emphasize the heightened obesity-related health risks associated with SO in the pediatric years.

Cow's Milk Bioactive Molecules in the Regulation of Glucose Homeostasis in Human and Animal Studies.

Obesity disrupts glucose metabolism, leading to insulin resistance (IR) and cardiometabolic diseases. Consumption of cow's milk and other dairy products may influence glucose metabolism. Within the complex matrix of cow's milk, various carbohydrates, lipids, and peptides act as bioactive molecules to alter human metabolism. Here, we summarize data from human studies and rodent experiments illustrating how these bioactive molecules regulate insulin and glucose homeostasis, supplemented with in vitro studies of the mechanisms behind their effects. Bioactive carbohydrates, including lactose, galactose, and oligosaccharides, generally reduce hyperglycemia, possibly by preventing gut microbiota dysbiosis. Milk-derived lipids of the milk fat globular membrane improve activation of insulin signaling pathways in animal trials but seem to have little impact on glycemia in human studies. However, other lipids produced by ruminants, including polar lipids, odd-chain, trans-, and branched-chain fatty acids, produce neutral or contradictory effects on glucose metabolism. Bioactive peptides derived from whey and casein may exert their effects both directly through their insulinotropic effects or renin-angiotensin-aldosterone system inhibition and indirectly by the regulation of incretin hormones. Overall, the results bolster many observational studies in humans and suggest that cow's milk intake reduces the risk of, and can perhaps be used in treating, metabolic disorders. However, the mechanisms of action for most bioactive compounds in milk are still largely undiscovered.

Differential effects of milk, yogurt, and cheese on energy homeostasis and brown adipose tissue phenotype in high-fat diet-induced obese mice.

Aim: We hypothesized that milk, yogurt, and cheese have differential impacts on energy expenditure (EE) and obesity in mice fed a high-fat diet (HFD). Methods: C57BL/6 mice (n = 16 per group) were fed a HFD or a HFD supplemented with fat-free milk (MILK), fat-free plain yogurt (YOG), or reduced-fat cheddar cheese (CHE; 19 kcal% fat), each provided at 10% of the daily energy intake, for 8 weeks. EE was quantified using a metabolic chamber. Metabolic pathways related to BAT mitochondrial function and uncoupling protein 1 (UCP1) abundance were assessed. Serum lipidomic profiles were analyzed to identify potential mediators of the observed effects. Results: MILK supplementation lowered weight gain and fat accumulation and enhanced EE and BAT thermogenesis, perhaps via the SIRT1-AMPK-PGC1α axis in BAT. This led to elevated UCP1 abundance and enhanced the abundance of hormone-sensitive lipase (HSL). MILK also altered serum lipid species, indicating enhanced energy use, and promoted BAT thermogenesis and mitochondrial function pathways. YOG exhibited a similar pattern but a lower magnitude of effects than MILK on reducing weight gain and fat mass, increasing EE, and BAT thermogenic proteins, including AMPK-PGC1α-UCP1. Both MILK and YOG showed a relative increase in serum PC 15:0_15:0 and LPC 15:0. In contrast, CHE reduced weight gain and increased EE without impacting BAT thermogenesis proteins or serum lipid species. Conclusion: Our study showed that MILK, YOG, and CHE reduced weight gain in mice on a HFD by increasing EE. MILK and YOG also up-regulated BAT thermogenesis, while both additionally altered lipids involved in fat metabolism and inflammation. CHE did not affect BAT thermogenesis and lipid species compared to HFD.

Isoferulic acid, a new anti-glycation agent, inhibits fructose- and glucose-mediated protein glycation in vitro.

The inhibitory activity of isoferulic acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25-5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Nε-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of ß-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.

Dietary Interventions for Type 2 Diabetes in South Asian Populations-A Systematic Review.

PURPOSE: South Asians face a high burden of type 2 diabetes (T2D). We systematically summarized current research on the efficacy, cultural relevance, and research gaps of nutrition interventions that could be used for treatment in this population. FINDINGS: We identified 18 articles published since 2010. Dietary pattern interventions have focused on low-glycemic index (GI) solutions and consistently reported improvement in glycemic management. Trials of nutrition education and counselling had diverse approaches, with those utilizing more intensive interventions generally eliciting better glycemic outcomes. Many studies developed interventions with cultural relevance by including traditional foods, providing materials in the local language, and acknowledging important food-related customs. These adaptations were seen in South Asian countries as well as Western countries hosting immigrants. Data from South Asian countries support low-GI and intensive counselling approaches for the treatment of T2D. Given the high prevalence of T2D in these populous countries, approaches that can reach large numbers of people are needed. In Western countries, more emphasis on providing culturally relevant nutrition therapy is needed.