Journal of Nutrition最新文献

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive condition that afflicts patients of all ages, including neonates. Previously, we reported that neonatal pigs fed formulas rich in medium-chain (MCFA) compared with those fed long-chain fatty acid (LCFA) for 21 d, developed panacinar steatosis with no changes in whole body obesity.

Objectives: The objective of the present study was to examine the temporal onset and development of NAFLD in neonatal pigs in response to MCFA feeding.

Methods: Neonatal pigs (n=18) were fed isocaloric MCFA or LCFA. Six pigs from each group were euthanized following 7, 14 or 21 d of feeding. Body composition was assessed before initiation and at the end of the feeding period using dual-energy X-ray absorptiometry. Liver fat content and liver morphological features were determined from photomicrographs and evaluated for NAFLD by a pathologist.

Results: Lean mass and fat mass as a percentage of body weight were not different between formulas. However, liver weight (P = 0.001) and liver fat mass (P < 0.001) were greater for pigs in the MCFA compared with those in the LCFA group. Steatosis developed as early as 7 d in the MCFA compared with the LCFA fed pigs (P < 0.001). In addition, steatosis progressed in a portal to venous direction as MCFA feeding duration was increased (P = 0.02). Pigs diagnosed with NASH (P < 0.001) and greater non-alcoholic fatty liver disease scores were those in the MCFA group (P < 0.001).

Conclusions: These results suggest that the onset and progression of NAFLD from steatosis to NASH occurs rapidly in response to MCFA feeding. Moreover, periportal steatosis is the initial feature in the development of NAFLD before its progression to NASH. The development of NAFLD in neonates seems to occur independently of whole-body adiposity.

Background: Secretory IgA (SIgA) is the first line of defense in protecting the intestinal epithelium against pathogenic bacteria, regulating gut microbiota composition, and maintaining intestinal homeostasis. Early weaning strategies may disrupt SIgA levels in piglet intestines, causing a decline in immune response and early weaning stress. However, the specific microbial mechanisms modulating SIgA in early-weaned piglets are not well understood.

Objective: We hypothesized that Akkermansia muciniphila increases intestinal SIgA production in the early-weaned piglets.

Methods: Fecal SIgA levels, SIgA-coated bacteria abundance, and fecal metagenomes were compared between 6 Huanjiang miniature (HM) and 6 Duroc×Landrace×Yorkshire (DLY) early-weaned piglets to identify bacterial species involved in SIgA modulation. 4 bacterial species were investigated using 5 groups (Control, A. muciniphila, L. amylovorus, L. crispatus, L. acidophilus) of male SPF C57BL/6J mice, weaned 3 weeks post-birth (n=8/group). Subsequently, 10-day-old Landrace×Yorkshire (LY) piglets were randomly assigned to three groups (Control, 10⁹A. muciniphila, 10⁸A. muciniphila) (n=10/group) to evaluate the effect of orally administered A. muciniphila on intestinal SIgA production and microbial composition.

Results: HM early-weaned piglets showed significantly higher SIgA levels (7.59 μg/mg, 95% CI: 3.2, 12, P = 0.002) and SIgA-coated bacteria abundance (8.64%, 95% CI: 3.2, 14, P = 0.014) than DLY piglets. In the mouse model, administration of A. muciniphila significantly increased SIgA levels (3.50 μg/mg, 95% CI: 0.59, 6.4, P = 0.018), SIgA-coated bacteria abundance (9.06%, 95% CI: 4, 14, P =0.018), and IgA⁺ plasma cell counts (6.1%, 95% CI: 4.3, 8, P = 0.005). In the pig experiments, oral administration of A. muciniphila to LY piglets significantly enhanced intestinal SIgA concentrations (4.22μg/mg, 95% CI: 0.37, 8.5, P = 0.034) and altered the SIgA-coated bacterial landscape.

Conclusion: Early intervention with A. muciniphila in nursing piglets can increases intestinal SIgA productionand alter the reactivity towards commensal bacteria upon early weaning.

Background: High intake of whole grains has consistently been associated with reduced risk of obesity, coronary heart disease, and type 2 diabetes. Dietary interventions have shown beneficial metabolic effects of whole grain, but the metabolic response varies with different types of cereals.

Objectives: We evaluate the metabolic effects of substituting refined wheat with wholegrain rye foods within a complex diet, examining day-long postprandial response of glucose-dependent insulinotropic peptide, (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, glucose, and inflammatory biomarkers in overweight and obese individuals.

Methods: Twenty-nine healthy adults, BMI 32 ± 9 kg/m² were randomly assigned to three intervention days, separated by one-week washout. Participants adhered to a hypocaloric diet rich in wholegrain rye for one intervention and refined wheat for the second intervention and were randomized to either diet for the third intervention with continuous blood sampling.

Results: No differences in GIP, GLP-1 or ghrelin levels were found between the diets when measured throughout the whole intervention day. GIP tAUC following the rye-based lunch was 31% (p < 0.05) lower compared with the wheat-based lunch and ghrelin concentrations were 29% (p < 0.05) lower after the rye-based dinner. Baseline HOMA-IR adjusted model, showed 61% (p = 0.015) lower whole-day GLP-1 and 40% (p = 0.03) lower GIP following the rye-based diet. Day-long glucose iAUC was 30% (p <0.001) lower following the rye-based diet and glycemic variability measured as SD reduced (-0.13 mmol/L p = 0.04). The rye-based diet vs refined wheat induced higher glycoprotein N-acetylation A by z-scores (0.36, p = 0.014).

Conclusions: Overall, no day-long differences in gut hormone levels were observed, but the wholegrain rye-based vs refined wheat-based dinner showed lower postprandial ghrelin concentrations. The rye-based diet improved day-long glycemic control in individuals with overweight and obesity. Observations of diet-induced inflammation following whole-grain rye intake warrant further investigation. THIS STUDY WAS PROSPECTIVELY REGISTERED AT CLINICALTRIALS.GOV (NCT05004584): https://clinicaltrials.gov/study/NCT05004584?locStr=Gothenburg,%20Sweden&country=Sweden&state=V%C3%A4stra%20G%C3%B6taland%20County&city=Gothenburg&distance=50&term=appetite&aggFilters=status:com&rank=1.

Background: In India, currently, there are no standard guidelines for the management of moderate acute malnutrition (MAM). Previous research in Bangladesh has shown that children with MAM have impaired gut microbiota development, and microbiota-directed complementary foods (MDCF) can potentially repair their gut microbiota.

Objectives: To evaluate the acceptability and safety of supplementing shelf-stable formulation of MDCF in Indian children with MAM as compared to a locally prepared ready-to-use supplementary food (RUSF) in three geographically distinct Indian populations and to establish and pilot systems of intervention delivery, collection, transport and storage of stool samples using stringent protocols.

Methods: This pre-proof of concept (prePOC), multicentric, open-labelled, age-stratified, randomised controlled trial was done in children aged 6-18 months with MAM. After a run-in period of 2 weeks, the participants were supplemented with MDCF or RUSF for 4 weeks through direct observation and followed up for another 2 weeks post intervention. Maternal responses to the acceptability of the organoleptic properties of supplements were recorded weekly during the intervention phase of 4 weeks. Compliance was reported based on the amount of supplement consumed by the children. Feasibility of weekly stool sample collection (except seventh week) within 30 minutes of passage was recorded. Anthropometric measurements were done at baseline and endline. Monitoring for adverse events was done throughout the course of the study.

Results: A total of 240 children with MAM were randomised to receive either MDCF or RUSF, of which 221 (92.1%) completed follow-up. The overall acceptability for more than 80% of the maternal responses was reported as good or very good for all organoleptic properties in both MDCF and RUSF arms. MDCF and RUSF interventions had good-to-high compliance in 83.0 % and 79.8% of participants, respectively. At the end of the intervention phase, 53.2% (58/109) children in MDCF arm against 42.0% (47/112) in RUSF arm had weight-for-length Z score >-2. The overall incidence of acute gastroenteritis reported was low; higher in MDCF compared to RUSF but not statistically significant.

Conclusion: The prePOC study demonstrates good acceptability and safety of MDCF amongst Indian children with MAM including the age group of 6-12 months of age. The study demonstrates feasibility to conduct a long-term supplementation study in this population.

Trial registration: Clinical trial registry of India (CTRI/2023/01/048716) STATEMENT OF SIGNIFICANCE: This study tested the acceptability and safety of MDCF in the Indian population and demonstrated the same in the 6 to <12 months age category, where it has not been tested elsewhere.

Riboflavin, commonly known as vitamin B₂, is an essential micronutrient critical for the function of flavoproteins, which utilize flavin mononucleotide and flavin adenine dinucleotide as cofactors in energy metabolism, lipid metabolism, redox regulation, and protein folding. Nutritional riboflavin deficiency has previously been observed in humans and animals, leading to adverse outcomes such as growth retardation, increased mortality, and liver damage, which may be attributed to apoptosis. While such deficiencies are now uncommon due to improved living standards, certain high-risk groups (e.g., those with chronic diseases, the elderly, and pregnant) have increased riboflavin demands, making them vulnerable to physiological riboflavin deficiency associated with apoptosis. Understanding the pathways through which riboflavin deficiency induces apoptosis, including mitochondrial dysfunction, endoplasmic reticulum stress, and reactive oxygen species, is essential for grasping its broader health impacts. Additionally, this deficiency disrupts fatty acid metabolism, potentially resulting in lipotoxic apoptosis. Despite its significance, riboflavin deficiency-induced apoptosis remains underexplored in the literature. Therefore, this review will discuss the roles of redox imbalance, mitochondrial dysfunction, endoplasmic reticulum stress, and lipotoxicity in apoptosis regulation due to riboflavin deficiency, aiming to highlight its importance for improving riboflavin nutrition and overall health.

Background: The carbon isotope ratio (CIR) is a candidate biomarker for sugar sweetened beverage (SSB) intake in the U.S. However, research specific to youth, who differ in their physiology and dietary patterns compared to adults, is lacking.

Objectives: We evaluated longitudinal associations of SSB intakes across childhood/adolescence with serum CIR. We also explored the relationship between other dietary intakes and serum CIR.

Methods: Data were from participants in two longitudinal, pediatric cohorts in Colorado: Exploring Perinatal Outcomes among CHildren Study (EPOCH) (visits at median 10 and 16 y, n=150) and Healthy Start Study (visits at median 5 and 9 y, n=166). Serum CIR was measured using isotope ratio mass spectrometry. Diet was assessed by food frequency questionnaires (EPOCH) or 24-hour diet recalls (Healthy Start). We assessed associations of longitudinal dietary intakes (log2-transformed, standardized) with serum CIR using linear mixed models adjusted for age, sex, and energy intake, and associations of change values between visits using linear regression models.

Results: In linear mixed models, higher SSB intake across visits was associated with higher serum CIR in both cohorts (β [95% CI]: 0.11[0.06,0.15] in EPOCH and 0.14[0.07,0.21] in Healthy Start). Higher meat intake and a higher dietary animal protein ratio were also positively associated with serum CIR in both cohorts (β [95% CI]: 0.08[0.05,0.12] and 0.18[0.13,0.23] in EPOCH; 0.08[0.01,0.16] and 0.28[0.21,0.35] in Healthy Start). In change analyses, there were positive associations for changes in the dietary animal protein ratio between visits with changes in serum CIR in both cohorts, but not for changes in SSB intake.

Conclusions: Our findings support serum CIR as a potential biomarker of SSB intake in youth cross-sectionally; however, there was not a strong link between change values over longer-term follow-up. Meat/animal protein intake was also consistently and, at times, more strongly associated with serum CIR.

Background: Although body fatness is a recognized risk factor for pancreatic ductal adenocarcinoma (PDAC), the underlying mechanisms of how fat composition affects pancreatic carcinogenesis are poorly understood. High fat diets (HFD) can disrupt intestinal barrier function, potentially accelerating carcinogenesis. Omega-3 (ω-3) polyunsaturated fatty acids (FAs) have anti-inflammatory properties and help preserve intestinal integrity.

Objective: to evaluate how ω-3 FAs affect the colonic barrier in the context of HFD-induced changes, in a mouse model of PDAC [p48-Cre; LSL-KrasG12D (KC)].

Methods: Male and female KC mice were randomized into one of four groups: i) a control diet containing approximately 11% total calories from fat with an ω-6:ω-3 FA ratio of 10:1 (C); ii) the control diet with high levels of ω-3 FA with an ω-6:ω-3 FA ratio of 1:1 (Cω3); iii) a HFD containing 60% total calories from fat with an ω-6:ω-3 FA ratio of approximately 10:1 (HF); iv) a HFD with high levels of ω-3 FA with an ω-6:ω-3 FA ratio of 1:1 (HFω3).

Results: Consumption of a HFD for 8 weeks caused: i) disruption of tight junction structure and function; ii) decreased Goblet cell number, iii) higher colonic TLR4 and NOX1 expression; iv) activation of TLR4-triggered pathways, i.e. NF-κB, JNK1/2; v) elevated plasma LPS levels; v) higher pancreatic TLR4 expression, and vi) accelerated acinar-to-ductal metaplasia. All of these events were mitigated in mice fed the HFω3.

Conclusions: Our findings support the concept that, in the context of obesity, ω-3 FA have protective effects during early-stage pancreatic carcinogenesis through the regulation of intestinal permeability and endotoxemia.

Background: Vegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 fatty acids, which elicits liver protection via interleukin-10 (IL10) in the murine model of PN.

Objective: In a preclinical model of PN in neonatal piglets, Vegaven was tested for efficacy and safety and compared with a mixed-oil lipid emulsion containing fish-oil (SMOFlipid).

Methods: 4-5-day-old male piglets were randomly allocated to isocaloric isonitrogenous PN for 14 days that varied only by the type of lipid emulsion (Vegaven, N=8; SMOFlipid, N=8). Hepatic IL10 tissue concentration served as primary outcome. Secondary outcomes were organ weights, bile flow, blood analyses, plasma insulin and glucagon concentrations, insulin signaling, proinflammatory cytokines, tissue lipopolysaccharide concentrations, and fatty acid composition of phospholipid fractions in plasma, liver, and brain.

Results: Total weight gain on trial, organ weights, and bile flow were similar between the Vegaven and the SMOFlipid group. Vegaven elicited higher hepatic IL10 (Δ=148 pg/mg protein, p<0.001) and insulin receptor substrate-2 levels (Δ=0.08 O.D., p=0.012). Plasma insulin concentrations (Δ=1.46 mU/L, p=0.003) and fructosamine (glycated albumin, Δ=12.4 μmol/g protein, p=0.003) were increased in SMOFlipid as compared with Vegaven group, indicating insulin resistance. Higher hepatic injury markers were observed more frequently in the SMOFlipid group compared with the Vegaven group. Lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 were increased in pancreatic and brain tissues of SMOFlipid- vs Vegaven-treated piglets. Insulin signaling was reduced in the brains of SMOFlipid-treated piglets. Vegaven and SMOFlipid elicited distinct fatty acid profiles in the phospholipid fractions of the rapidly growing brains, but showed similar accretion of docosahexaenoic acid and arachidonic acid after two weeks of PN.

Conclusions: Vegaven was well tolerated in this piglet model of PN and demonstrated distinct biological actions compared with SMOFlipid, namely lower liver, pancreas, and brain inflammation, enhanced insulin signaling, and improved whole-body glucose control.

Background: Low phosphorus (LP) diets perturb hepatic energy metabolism homeostasis in fish. However, the specific mechanisms in LP-induced hepatic energy metabolism disorders remain to be fully elucidated.

Objectives: This study sought to elucidate the underlying mechanisms of mitochondria involved in LP-induced energy metabolism disorders.

Methods: Spotted seabass were fed diets with 0.72% (S-AP, control) or 0.36% (S-LP) available phosphorus for 10 weeks. Drp1 was knocked down or protein kinase A (PKA) was activated using 8Br-cAMP (5 μM, a PKA activator) in spotted seabass hepatocytes under LP medium. Zebrafish were fed Z-LP diets (0.30% available phosphorus) containing Mdivi-1 (5 mg/kg, a Drp1 inhibitor) or 8Br-cAMP (0.5 mg/kg) for 6 weeks. Biochemical and molecular parameters, along with transmission electron microscopy and immunofluorescence, were used to assess hepatic glycolipid metabolism, mitochondrial function and morphology.

Results: Spotted seabass fed S-LP diets showed reduced ATP (0.52-fold) and cyclic adenosine monophosphate (cAMP) (0.52-fold) levels, along with reduced Drp1 (s582) (0.38-fold) and PKA (0.61-fold) phosphorylation levels in the liver compared with those fed S-AP diets (P < 0.05). Drp1 knockdown elevated ATP levels (1.99-fold), decreased mitochondrial DRP1 protein levels (0.45-fold), and increased mitochondrial aspect ratio (1.82-fold) in LP-treated hepatocytes (P < 0.05). Furthermore, 8Br-cAMP-treated hepatocytes exhibited higher PKA phosphorylation (2.85-fold), ATP levels (1.60-fold), and mitochondrial aspect ratio (2.00-fold), along with decreased mitochondrial DRP1 protein levels (0.29-fold) under LP medium (P < 0.05). However, mutating s582 to alanine mimic Drp1 dephosphorylation decreased ATP levels (0.63-fold) and mitochondrial aspect ratio (0.53-fold) in 8Br-cAMP-treated hepatocytes (P < 0.05). In addition, zebrafish were fed Z-LP diets containing Mdivi-1 or 8Br-cAMP had higher ATP levels (3.44-fold or 1.98-fold) than that fed Z-LP diets (P < 0.05).

Conclusions: These findings provide a potential mechanistic elucidation for LP-induced energy metabolism disorders through the cAMP/PKA/Drp1-mediated mitochondrial fission signaling pathway.