Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

Early life stress (ELS) and a Western diet (WD) promote mood and cardiovascular disorders, however, how these risks interact in disease pathogenesis is unclear. We assessed effects of ELS with or without a subsequent WD on behaviour, cardiometabolic risk factors, and cardiac function/ischaemic tolerance in male mice. Fifty-six new-born male C57BL/6J mice were randomly allocated to a control group (CON) undisturbed before weaning, or to maternal separation (3h/day) and early (postnatal day 17) weaning (MSEW). Mice consumed standard rodent chow (CON, n = 14; MSEW, n = 15) or WD chow (WD, n = 19; MSEW + WD, n = 19) from week 8 to 24. Fasted blood was sampled and open field test and elevated plus maze (EPM) tests undertaken at 7, 15, and 23 weeks of age, with hearts excised at 24 weeks for Langendorff perfusion (evaluating pre- and post-ischaemic function). MSEW alone transiently increased open field activity at 7 weeks; body weight and serum triglycerides at 4 and 7 weeks, respectively; and final blood glucose levels and insulin resistance at 23 weeks. WD increased insulin resistance and body weight gain, the latter potentiated by MSEW. MSEW + WD was anxiogenic, reducing EPM open arm activity vs. WD alone. Although MSEW had modest metabolic effects and did not influence cardiac function or ischaemic tolerance in lean mice, it exacerbated weight gain and anxiogenesis, and improved ischaemic tolerance in WD fed animals. MSEW-induced increases in body weight (obesity) in WD fed animals in the absence of changes in insulin resistance may have protected the hearts of these mice.

Diets and dietary constituents that we consume have a considerable impact on disease risk. Intriguingly these effects may be modulated to some extent by sex. Lack of female representation in nutritional studies as well as a lack of stratification by sex has and continues to limit our understanding of these sex × diet interactions. Here we provide an overview of the current and available literature describing how exposure to certain dietary patterns (Western-style diet, Mediterranean diet, vegetarian/vegan, ketogenic diet) and dietary constituents (dietary fibre, PUFA and plant bioactive) influences disease risk in a sex-specific manner. Interestingly, these sex differences appear to be highly disease-specific. The identification of such sex differences in response to diet stresses the importance of sex stratification in nutritional research.

Obese mothers’ offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers’ offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.

The present study examines the association of diet with depressive symptoms among stroke survivors from a community cohort of older adults. Depression is common after stroke. A healthy diet has previously been associated with fewer depressive symptoms in older individuals, but it is unknown if this effect is also seen in stroke survivors. Eighty-six participants from the Memory and Aging Project with a history of stroke at their study baseline enrolment, complete dietary data and two or more assessments for depression were included in this observational prospective cohort analysis. Depressive symptoms were assessed annually with a 10-item version of the Center for Epidemiologic Studies Depression scale. Diet was assessed using a validated food-frequency questionnaire administered at baseline. Diet scores were based on analysis of participants’ reported intakes of 144 food items. A generalised estimating equation (GEE) model was applied to examine the association of diet score with depressive symptoms. The study participants had a mean age of 82 ± 7⋅17 years and 14⋅42 ± 2⋅61 years of education, and 82⋅56 % were female. Western diet score was positively associated with depressive symptoms over time (diet score tertile 3 v. tertile 1: β = 0⋅22, se = 0⋅09, P = 0⋅02; P for trend = 0⋅022). Interaction with sex suggested a stronger effect in females. A Western diet was associated with more post-stroke depressive symptoms, suggesting nutrition is important not only for reducing cerebrovascular risk, but for protecting post-stoke mental health as well.

There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

Dietary patterns influence gut microbiota composition. To date, there has not been an assessment of diet and gut microbiota in Veterans, who have a history of unique environmental exposures, including military deployment, that may influence associations between diet and gut microbiota. Our aim was to characterise Veteran habitual dietary intake and quality, and to evaluate correlations between diet and gut microbiota. We administered Food Frequency Questionnaires (FFQs) and collected stool samples from 330 Veterans. FFQ data were used to generate Healthy Eating Indices (HEI) of dietary quality. Exploratory factor analysis was used to identify two dietary patterns we defined as “Western” and “Prudent.” Stool samples underwent 16S rRNA gene sequencing, and the resulting data were used to evaluate associations with dietary variables/indices. Analyses included linear regression of α-diversity, constrained analysis of principal coordinates of β-diversity, and multivariate association with linear models and Analysis of Composition of Microbiomes analyses of dietary factors and phylum- and genus-level taxa. There were no significant associations between dietary patterns or factors and α- or β-diversity. At the phylum level, increasing HEI scores were inversely associated with relative abundance of Actinobacteria, and added sugar was inversely associated with abundance of Verrucomicrobia. Veterans largely consumed a Western-style diet, characterised by poor adherence to nutritional guidelines.

We aimed to fully review the association of empirical dietary patterns with the risk of non-communicable chronic diseases and to rate the quality of the evidence. Published meta-analyses of observational studies investigating the association of empirically derived dietary patterns with the risk of chronic diseases were identified by searching PubMed and Scopus till September 2019. Two independent reviewers extracted the information and rated the quality of the evidence by NutriGrade score. For each meta-analysis, cross-sectional and case–control studies were excluded and then summary relative risk was recalculated by using a random-effects model. Sixteen meta-analyses of prospective cohort studies, reporting eighteen SRR for healthy dietary patterns and sixteen SRR for unhealthy patterns obtained from 116 primary prospective cohort studies with 4·8 million participants, were included. There was moderate quality of evidence for the inverse association of healthy dietary patterns with the risk of type 2 diabetes (T2D), fracture and colorectal and breast cancers. There was also low-quality evidence for the inverse relation between healthy dietary patterns and the risk of all-cause and cardiovascular mortality, depression, CHD and respiratory diseases. There was moderate quality of evidence for a positive association between unhealthy dietary patterns and the risk of T2D, fracture and the metabolic syndrome. Adopting a healthy dietary pattern may reduce the risk of T2D, CHD and premature death. More research is needed for outcomes for which the quality of the evidence was rated low, such as respiratory disease, mental illness and site-specific cancers.

The aim of this study was to develop a purified diet that mimics the characteristics of the Japanese diet using readily available materials with a simpler composition and a focus on quality, with the goal of facilitating performance of studies on the Japanese diet worldwide. The utility of the new diet was examined as a mimic of the standard Japanese diet for use in animal experiments. We examined whether a key characteristic of the Japanese diet of being less likely to cause obesity could be reproduced. The mimic diet had a balance of protein, fat and carbohydrate based on the 1975 Japanese diet, which is the least likely to cause obesity, and materials chosen with reference to the National Health and Nutrition Survey (NHNS). To examine similarities of the mimic diet with the model 1975 Japanese diet, we created a menu of the 1975 diet based on the NHNS and prepared the freeze-dried and powdered diet. The mimic diet, the 1975 Japanese diet, a control AIN-93G diet and a Western diet were fed to mice for 4 weeks. As a result, the mimic diet and the 1975 diet resulted in less accumulation of visceral fat and liver fat. Mice given these two diets showed similar effects. This indicates that the mimic diet used in this study has characteristics of the 1975 Japanese diet and could be used as a standard Japanese diet in animal experiments.

Micronutrient deficiencies contribute to many age-related disorders. One group at particular risk of micronutrient deficiencies is the elderly. Many elderly, such as the frail and those living in institutions, rely on ready meals of variable, often poor, nutritional quality for a significant part of their daily nutritional needs. New policies are needed to ensure that micronutrients (vitamins and minerals) and phytochemicals of known nutritional value are retained during the manufacture of ready meals. This together with increased awareness of the importance of micronutrients for health, and simple, clear labelling of the micronutrient content of ready meals would help in the choice of healthier products. Professionally prepared ready meals monitored by nutritionists and dietitians can help achieve these goals so that ready meals become part of the solution to poor nutrition in the elderly, rather than being viewed as part of the problem.

A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague–Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P<0·05) and Tnfα, and of toll-like receptor 4 (Tlr4) (P<0·05). Cit also improved plasma TAG and insulin levels. In the colon, it decreased inflammation (Tnfα and Tlr4 expressions) and increased claudin-1 protein expression. This was associated with higher levels of Bacteroides/Prevotella compared with rats fed the Western diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity and is now the most common chronic liver disease in developed countries. NAFLD is defined as excessive accumulation of lipid in the liver, i.e. hepatosteatosis. The severity of NAFLD ranges from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH). Simple steatosis is relatively benign until it progresses to NASH, which is characterised by hepatic injury, inflammation, oxidative stress and fibrosis. Hepatic fibrosis is a risk factor for cirrhosis and primary hepatocellular carcinoma. Our studies have focused on the impact of diet on the onset and progression of NASH. We developed a mouse model of NASH by feeding Ldlr−/− mice a western diet (WD), a diet moderately high in saturated and trans-fat, sucrose and cholesterol. The WD induced a NASH phenotype in Ldlr−/− mice that recapitulates many of the clinical features of human NASH. We also assessed the capacity of the dietary n-3 PUFA, i.e. EPA (20 : 5,n-3) and DHA (22 : 6,n-3), to prevent WD-induced NASH in Ldlr−/− mice. Histologic, transcriptomic, lipidomic and metabolomic analyses established that DHA was equal or superior to EPA at attenuating WD-induced dyslipidemia and hepatic injury, inflammation, oxidative stress and fibrosis. Dietary n-3 PUFA, however, had no significant effect on WD-induced changes in body weight, body fat or blood glucose. These studies provide a molecular and metabolic basis for understanding the strengths and weaknesses of using dietary n-3 PUFA to prevent NASH in human subjects.

Diet-induced obesity in mice can be achieved through the use of diets with different macronutrient compositions and textures. We aimed at determining the contribution of macronutrient composition to obesity development and associated pathophysiological changes in mice. C57BL/6N mice were offered a control, a high-fat or a Western-style diet, either as pellet (H for hard) or with identical composition in powder form (S for soft), resulting in C-S, C-H, HF-H, HF-S, W-H and W-S groups, respectively. Body fat distribution, expression levels of selected target genes in adipose tissues, clinical chemistry and hormone concentration in the blood, as well as liver TAG content were measured. The most striking finding was that all mice fed the different powder diets developed obesity with similar weight gain, whereas among the mice fed the pellet diets, only those given the HF and W diets became obese. This allowed us to separate diet-specific effects from obesity-mediated effects. Irrespective of the food texture, the W diet induced a more severe hepatosteatosis and higher activities of serum transaminases compared with the two other diets. Adipose tissue gene expression analysis revealed that leptin and adiponectin levels were not affected by the dietary composition per se, whereas uncoupling protein 1 and 11β-hydroxysteroid dehydrogenase type 1 levels were decreased by both dietary composition and changes in body weight. In conclusion, diets differing in macronutrient composition elicit specific pathophysiological changes, independently of changes in body weight. A diet high in both fat and sugars seems to be more deleterious for the liver than a HF diet.

Certain dietary patterns may be related to the risk of CVD. We hypothesised that a plant-centred dietary pattern would be associated with a reduced risk of first myocardial infarction (MI). A case–control study of Norwegian men and postmenopausal women (age 45–75 years) was performed. A FFQ was administered, generally within 3 d after incident MI (n 106 cases). Controls (n 105) were frequency matched on sex, age and geographic location. On the FFQ, 190 items were categorised into thirty-five food groups and an a priori healthy diet pattern score was created. We estimated OR using logistic regression with adjustment for energy intake, family history of heart disease, marital status, current smoking, education and age. Among food groups, the risk of MI was significantly higher per sd of butter and margarine (OR 1·66 (95 % CI 1·12, 2·46)), and lower per sd of tomatoes (OR 0·53 (95 % CI 0·35, 0·79)), high-fat fish (OR 0·57 (95 % CI 0·38, 0·86)), wine (OR 0·58 (95 % CI 0·41, 0·83)), salad (OR 0·59 (95 % CI 0·40, 0·87)), wholegrain breakfast cereals (OR 0·64 (95 % CI 0·45, 0·90)), cruciferous vegetables (OR 0·66 (95 % CI 0·47, 0·93)) and non-hydrogenated vegetable oil (OR 0·68 (95 % CI 0·49, 0·95)). An abundance of cases were found to have a low a priori healthy diet pattern score. A dietary pattern emphasising nutrient-rich plant foods and high-fat fish and low in trans fatty acids was associated with decreased risk of MI among Norwegians.