Postnatal Consumption of Black Bean Powder Protects against Obesity and Dyslipidemia in Male Adult Rat Offspring from Obese Pregnancies.

The adverse influence of maternal obesity on offspring metabolic health throughout the life-course is a significant public health challenge with few effective interventions. We examined if black bean powder (BBP) supplementation to a high-calorie maternal pregnancy diet or a postnatal offspring diet could offer protection against the metabolic programming of metabolic disease risk in adult offspring. Female Sprague Dawley rats were randomly assigned to one of three diets (n = 10/group) for a 3-week pre-pregnancy period and throughout gestation and lactation: (i) a low-caloric control diet (CON); (ii) a high-caloric obesity-inducing diet (HC); or (iii) the HC diet with 20% black bean powder (HC-BBP). At weaning [postnatal day (PND) 21], one male pup from each dam was weaned onto the CON diet throughout the postnatal period until adulthood (PND120). In addition, a second male from the HC group only was weaned onto the CON diet supplemented with BBP (CON-BBP). Thus, based on the maternal diet exposure and offspring postnatal diet, four experimental adult offspring groups were compared: CON/CON, HC/CON, HC-BPP/CON, and HC/CON-BBP. On PND120, blood was collected for biochemical analysis (e.g., lipids, glycemic control endpoints, etc.), and livers were excised for lipid analysis (triglycerides [TG] and cholesterol) and the mRNA/protein expression of lipid-regulatory targets. Compared with the CON/CON group, adult offspring from the HC/CON group exhibited a higher (p < 0.05) body weight (BW) (682.88 ± 10.67 vs. 628.02 ± 16.61 g) and hepatic TG (29.55 ± 1.31 vs. 22.86 ± 1.85 mmol/g). Although maternal BBP supplementation (HC-BBP/CON) had little influence on metabolic outcomes, the consumption of BBP in the postnatal period (HC/CON-BBP) lowered hepatic TG and cholesterol compared with the other treatment groups. Reduced hepatic TG in the HC/CON-BBP was likely associated with lower postnatal BW gain (vs. HC/CON), lower mRNA and protein expression of hepatic Fasn (vs. HC/CON), and lower serum leptin concentration (vs. CON/CON and HC groups). Our results suggest that the postnatal consumption of a black-bean-powder-supplemented diet may protect male rat offspring against the programming of obesity and dyslipidemia associated with maternal obesity. Future work should investigate the bioactive fraction of BBP responsible for the observed effect.

Bean Consumption during Childhood Is Associated with Improved Nutritional Outcomes in the First Two Years of Life.

Bean consumption during childhood may play a role in promoting early-life health given their high nutritional quality. To examine the associations of children's bean consumption with the socio-demographic characteristics of the child and mother and the child's nutrient intake, we analyzed data from the WIC-ITFPS-2, which followed children and their mothers at 1, 3, 5, 7, 9, 11, 13, 15, 18, and 24 months (m) following birth. Caregivers (mostly mothers) responded to an interview-administered 24 h recall on their child's dietary intake at each time point. The intake of dried beans, chili, yellow beans, and lima beans was quantified. Correlate measures included socio-demographic characteristics. Outcome measures of interest focused on the intake of macronutrients (grams and % kcals) and micronutrients at 11 (infancy) and 24 m (toddler) only. To ensure statistical power, we only examined the associations of dried beans and chili with socio-demographics (Chi-square tests) and nutritional outcomes (ANOVA) at 11 and 24 m. The proportion of children who consumed dried beans or chili was very low in the first 6 m of age, started to increase at 7 m (1.2% and 0.4%) and 11 m (4.9% and 2.3%), and reached a high level at 18 m (10.5%) and 24 m (5.9%), respectively. Consumption of yellow or lima beans was rare (<0.1%). At 11 and 24 m, dried bean consumption was higher in children who were White (vs. Black). Dried bean and chili consumption was higher in children who were of Hispanic or Latino ethnicity (vs. non-Hispanic or non-Latino ethnicity). Children who consumed dried beans and chili at 11 or 24 m had a higher intake of total energy, protein, total fiber, potassium, folate, and magnesium compared with non-consumers. The bean consumption was low amongst children, differed by race and ethnicity, and was associated with improved macro- and micronutrient intake in children at 11 and 24 m.

Maternal Bean Consumption during Pregnancy: Distribution and Nutritional Outcomes.

(1) Background: Due to their high nutritional value, we aimed to characterize the frequency and amount of maternal consumption of beans during pregnancy and their associations with diet quality and nutrient intake. (2) Methods: We conducted a secondary data analysis of US pregnant women (n = 1444) from the Infant Feeding Practices Study II, a longitudinal study that followed mother-infant pairs from late pregnancy to 1 year postpartum. Maternal bean intake (food types [dried beans, chili, and bean soup], frequency, serving size, and amount), diet quality (Healthy Eating Index [HEI]), and nutrient intake were estimated with a Food Frequency Questionnaire taken in the third trimester of pregnancy. Associations of bean consumption with diet quality and nutrient intake were examined with analysis of variance, Fisher's least significant difference tests, correlation coefficients, and coefficients of determination. (3) Results: In general, maternal bean consumption was low during pregnancy: 0.31 cups/week of dried beans, 0.37 cups/week of chili, and 0.10 cups/week of bean soup. Maternal bean consumption varied by socio-demographics and geographic regions. In comparison with those who never consumed dried beans, mothers who ate dried beans ≥ 1 time per week had a higher mean HEI score (67.5 vs. 63.6), intake of total fiber (24.4 vs. 17.4 g/day), and protein (93.4 vs. 79.9 g/day), but a lower percentage of energy from added sugar (12.6 vs. 15.2%). Higher dried bean consumption had weak-to-moderate correlations with intake of total fiber (correlation coefficient, 0.320), insoluble fiber (0.316), soluble fiber (0.310), and folate (0.286). Similar but less extensive correlations were observed for chili and bean soup consumption. (4) Conclusions: In this US cohort of pregnant women, bean consumption was low. Increased intake of beans (≥1 time per week) may improve maternal diet quality during pregnancy.

Egg Introduction during Infancy is Associated with Lower Fat Mass Index in Females at Early Adolescence.

BACKGROUND: Egg consumption may play an important role in early-life growth given their high-quality protein, essential fatty acids, and micronutrients. OBJECTIVES: Study objectives were to examine the longitudinal associations of infant age at egg introduction with obesity outcomes in early childhood, middle childhood (mid-childhood), and early adolescence. METHODS: We used existing data from 1089 mother-child dyads from Project Viva to estimate age at egg introduction through a questionnaire completed by mothers at ∼1 y postpartum (mean ± SD, 13.3 ± 1.2 mo). Outcome measures included height and weight (early childhood, mid-childhood, and early adolescence), body composition including total fat mass, trunk fat mass, and lean mass (mid-childhood and early adolescence), and plasma adiponectin and leptin (early and mid-childhood and early adolescence). We defined childhood obesity as sex- and age-specific BMI ≥ 95th percentile. We estimated the associations of infant age at egg introduction with risk of obesity using multivariable logistic regression and multivariable linear regression models for BMI-z-score, body composition measures, and adiposity hormones; adjusted for maternal prepregnancy BMI and sociodemographics. RESULTS: Among females, those introduced to egg by the 1-y survey had a lower total fat mass index (confounder-adjusted mean difference, -1.23 kg/m2; 95% CI: -2.14, -0.31), and trunk fat mass index (confounder-adjusted mean difference, -0.57 kg/m2; 95% CI: -1.01, -0.12) in early adolescence compared to those not introduced (reference group). However, no associations between infant age at egg introduction and risk of obesity were observed among males (confounder-adjusted odd ratio [aOR], 1.97; 95% CI: 0.90, 4.30) or females (aOR, 0.68; 95% CI: 0.38, 1.24) across all ages. Egg introduction in infancy was associated with lower plasma adiponectin among females (confounder-adjusted mean difference, -1.93 µg/mL; 95% CI: -3.70, -0.16) in early childhood only. CONCLUSIONS: Egg introduction during infancy among females is associated with lower total fat mass index in early adolescence and plasma adiponectin in early childhood. This trial was registered at clinicaltrials.gov as NCT02820402.

Frequency of Infant Egg Consumption and Risk of Maternal-Reported Egg Allergy at 6 Years.

BACKGROUND: Recent research suggests that early egg introduction during infancy may help to prevent egg allergy development. However, the infant egg consumption frequency that is sufficient to induce this immune tolerance remains uncertain. OBJECTIVES: We examined the associations between the infant egg consumption frequency and maternal-reported child egg allergy at 6 y. METHODS: We analyzed data of 1252 children from the Infant Feeding Practices Study II (2005-2012). Mothers reported the frequency of infant egg consumption at 2, 3, 4, 5, 6, 7, 9, 10, and 12 mo old. Mothers reported the status of their child's egg allergy at the 6-y follow-up. We used Fisher exact test, Cochran-Armitage Trend Test, and log Poisson regression models to compare 6-y egg allergy risk by the frequency of infant egg consumption. RESULTS: The risk of maternal-reported egg allergy at 6 y significantly (P-trend = 0.004) decreased with infant egg consumption frequency at 12 mo: 2.05% (11/537) for infants not consuming eggs, 0.41% (1/244) for those consuming eggs <2 times per wk, and 0.21% (1/471) for those consuming eggs ≥2 times per wk. A similar but nonsignificant trend (P-trend=0.109) was observed for egg consumption at 10 mo (1.25%, 0.85%, and 0%, respectively). After adjusting for socioeconomic confounders, breastfeeding, complementary food introduction, and infant eczema, infants who consumed eggs ≥2 times per wk at 12 mo had a significantly lower RR of maternal-reported egg allergy at 6 y (confounder-adjusted RR: 0.11; 95% CI: 0.01, 0.88; P = 0.038), whereas those who consumed <2 times per wk (confounder-adjusted RR: 0.21; 95% CI: 0.03, 1.67; P = 0.141) did not have a significantly lower risk than those who did not consume eggs at all. CONCLUSIONS: Consumption of eggs ≥2 times per wk in late infancy is associated with a reduced risk of developing egg allergy later in childhood.

A pilot study of the association between maternal mid-pregnancy cholesterol and oxysterol concentrations and labor duration.

BACKGROUND: Previous animal model studies have highlighted a role for cholesterol and its oxidized derivatives (oxysterols) in uterine contractile activity, however, a lipotoxic state associated with hypercholesterolemia may contribute to labor dystocia. Therefore, we investigated if maternal mid-pregnancy cholesterol and oxysterol concentrations were associated with labor duration in a human pregnancy cohort. METHODS: We conducted a secondary analysis of serum samples and birth outcome data from healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation. Serum was analyzed for total-C, HDL-C, and LDL-C by direct automated enzymatic assay and oxysterol profile including 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24-hydroxycholesterol (24OHC), 25-hydroxycholesterol (25OHC), 27-hydroxycholesterol (27OHC), and 7-ketocholesterol (7KC) by liquid chromatography-selected ion monitoring-stable isotope dilution-atmospheric pressure chemical ionization-mass spectroscopy. Associations between maternal second trimester lipids and labor duration (minutes) were assessed using multivariable linear regression adjusting for maternal nulliparity and age. RESULTS: An increase in labor duration was observed for every 1-unit increment in serum 24OHC (0.96 min [0.36,1.56], p < 0.01), 25OHC (7.02 min [1.92,12.24], p = 0.01), 27OHC (0.54 min [0.06, 1.08], p < 0.05), 7KC (8.04 min [2.7,13.5], p < 0.01), and total oxysterols (0.42 min [0.18,0.06], p < 0.01]. No significant associations between labor duration and serum total-C, LDL-C, or HDL-C were observed. CONCLUSIONS: In this cohort, mid-pregnancy concentrations of maternal oxysterols (24OHC, 25OHC, 27OHC, and 7KC) were positively associated with labor duration. Given the small population and use of self-reported labor duration, subsequent studies are required for confirmation.

Maternal Pea Protein Intake Provides Sex-Specific Protection against Dyslipidemia in Offspring from Obese Pregnancies.

Increased consumption of dietary pulse protein has been shown to assist in body weight regulation and improve a range of metabolic health outcomes. We investigated if the exchange of casein for yellow pea protein (YPPN) in an obese-inducing maternal diet throughout pregnancy and lactation offered protection against obesity and dyslipidemia in offspring. Sixty female Sprague Dawley rats were fed a low-calorie control diet (CON), a high-caloric obesity-inducing diet (with casein protein (CP), HC-CP), or an isocaloric/macronutrient-matched HC diet supplemented with YPPN isolate (HC-PPN) in pre-pregnancy, gestation, and lactation. Body weight (BW) and metabolic outcomes were assessed in male and female offspring at weaning and in adulthood after consuming the CON diet in the postnatal period. Consumption of the HC-PPN diet did not protect against maternal obesity but did improve reproductive success compared with the HC-CP group (72.7% versus 43.7%) and reduced total energy, fat, and protein in maternal milk. Male, but not female, offspring from mothers fed the HC-CP diet demonstrated hyperphagia, obesity, dyslipidemia, and hepatic triglyceride (TG) accumulation as adults compared with CON offspring. Isocaloric exchange of CP for YPPN in a high-calorie obese-inducing diet did not protect against obesity but did improve several aspects of lipid metabolism in adult male offspring including serum total cholesterol, LDL/VLDL cholesterol, triglycerides (TGs), and hepatic TG concentration. Our results suggest that the exchange of CP for YPPN in a maternal obese-inducing diet selectively protects male offspring from the malprogramming of lipid metabolism in adulthood.

Delayed egg introduction beyond infancy and increased egg allergy risk in childhood.

AIM: Egg is a major food allergen in childhood. Recent studies suggest that early introduction of allergenic foods can decrease the risk of developing egg allergy. The impact of early egg introduction in the general population is unclear. We examined associations between age of infant egg introduction and childhood egg allergy outcomes in a general population. METHODS: The study population consisted of 1217 neonates from Project Viva, a longitudinal pre-birth cohort in eastern Massachusetts area, USA. Mothers reported age of infant egg introduction and child egg allergy using questionnaires and specific IgE to egg white was assayed. We estimated associations between age of infant egg introduction and egg allergy outcomes using Log-binomial regression models, adjusting for socio-demographics and health confounders. RESULTS: Egg allergy at 2 years was significantly higher (8.0% vs. 1.4%, P < 0.0001) in children who had delayed egg introduction beyond infancy, compared with children who were introduced to egg during infancy (adjusted relative risk or aRR 7.58; 95% CI 3.08, 18.61). At 12 years, the risk of egg allergy remained significantly higher (3.9% vs. 1.1%, P = 0.048) in children with delayed egg introduction compared with children introduced to egg during infancy (aRR 4.07; 95% CI 1.20, 13.87). CONCLUSIONS: Infants with delayed introduction of eggs after 12 months had increased risk of egg allergy in childhood (2 years) and the relationship persisted in early adolescence (12 years). Our findings suggest that introduction to eggs before 12 months could contribute to the prevention of egg allergy.

Maternal pea fiber supplementation to a high calorie diet in obese pregnancies protects male offspring from metabolic dysfunction in adulthood.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Infant age at egg introduction and malnutrition-related child growth in the United States.

To evaluate the relationship between infant age of egg introduction and malnutrition-related growth outcomes in the United States, we analysed secondary data of 1716 mother-child dyads in the Infant Feeding Practices Study II and its Year 6 Follow-Up Study. Malnutrition-related growth outcomes included body mass index z-score (BMIZ), obesity (weight-for-height z-score [WHZ] ≥3 or BMIZ ≥ 2), WHZ, wasting (WHZ < -2), height-for-age z-score (HAZ), and stunting (HAZ < -2). Infant age at egg introduction was analysed as a continuous variable. We used generalised estimating equations to estimate the mean difference in continuous outcomes and relative risk [RR]) for binary outcomes, adjusting for related maternal and child confounders. We also explored interactions with child sex, maternal race/ethnicity, maternal educational level, ever breastfeeding, and formula feeding. In the total sample, a later infant age at egg introduction was associated with a lower mean difference in HAZ (confounder-adjusted mean difference = -0.08, 95% confidence interval [CI]: -0.12 to -0.03 per month) and a higher risk of stunting (confounder-adjusted RR = 1.17, 95% CI: 1.03-1.33 per month) at 6 years. The associations between infant age at egg introduction and 12-month growth outcomes differed by child sex. Among females but not among males, later introduction of eggs was associated with a lower mean WHZ (-0.06 [-0.12 to 0.00] per month) at 12 months. Later egg introduction during infancy was associated with a lower mean HAZ and a higher risk of stunting in 6-year-old children. Besides this, it was associated with a lower WHZ among females at 12 months.

Associations of maternal lipoprotein particle distribution in mid-pregnancy with birth outcomes: a pilot study.

BACKGROUND: An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes. METHODS: We conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy. Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI. RESULTS: Although conventional lipids were not associated (p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted ß-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted ß-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI. CONCLUSION: The preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth.

Saturated Fat and Cardiovascular Health: Phenotype and Dietary Factors Influencing Interindividual Responsiveness.

PURPOSE OF REVIEW: Recent inconsistencies in nutrition research studies examining the influence of saturated fat (SFA) on cardiovascular disease (CVD) risk have led to substantial scientific debate and increased public confusion. This review will summarize metabolic characteristics and food-based factors that underlie interindividual responsiveness to SFA consumption. RECENT FINDINGS: The magnitude of postprandial blood lipid responses to SFA intake is dependent on a number of individual factors including age, sex, and adiposity status. Further, the metabolic effects of SFA intake are influenced by the specific types of SFAs and the food matrix within which they are contained. Importantly, results from research examining the effects of SFA on CVD risk should be interpreted with consideration of the comparator nutrient (i.e., carbohydrate, monounsaturated fat, polyunsaturated fat). A more nuanced understanding of the multitude of factors mediating the influence of SFA on lipid metabolism and CVD risk might help resolve the current controversy and inform more precise personalized recommendations for future dietary guidelines.

Gestational hypercholesterolemia programs hepatic steatosis in a sex-specific manner in ApoE-deficient mice.

Maternal hypercholesterolemia (MHC), a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy, may influence offspring hepatic lipid metabolism and increase the risk of nonalcoholic fatty liver disease (NAFLD). As NAFLD is characterized by a sexual dimorphic response, we assessed whether early-life exposure to excessive cholesterol influences the development of NAFLD in offspring and whether this occurs in a sex-specific manner. Female apoE-/- mice were randomly assigned to a control (CON) or a high cholesterol (CH; 0.15%) diet prior to breeding. At parturition, a cross-fostering approach was used to establish three groups: (1) normal cholesterol exposure throughout gestation and lactation (CON-CON); (2) excessive cholesterol exposure throughout gestation and lactation (CH-CH); and (3) excessive cholesterol exposure in the gestation period only (CH-CON). Adult male offspring (PND 84) exposed to excessive cholesterol during gestation only (CH-CON) demonstrated hepatic triglyceride (TG) accumulation and reduced lipogenic gene expression. However, male mice with a prolonged cholesterol exposure throughout gestation and lactation (CH-CH) had a similar, but not exacerbated hepatic response. Further, with the exception of higher serum TG in adult CH-CH females, evidence for a programming effect in female offspring was largely absent in comparison with males. These results indicate a sexual dimorphic response with respect to the effect of MHC on later life hepatic steatosis and highlight the gestation period as the most influential malprogramming window for hepatic lipid dysfunction in males.

Three-Day Dietary Manipulation in Multiple Sclerosis: Exercise and Fatigue Outcomes.

BACKGROUND: In persons with multiple sclerosis (MS), the effect of nutrition on exercise performance and fatigue remains unknown. The objective was to determine whether a 3-day diet high in triglycerides (FAT) compared with a 3-day diet high in carbohydrates (CARB) would improve fatigue and exercise performance in persons with MS. METHODS: A randomized controlled crossover design was incorporated to study FAT versus CARB on submaximal cycling endurance (60% of peak oxygen consumption), substrate utilization, and fatigue in 12 persons with mild-to-moderate MS (Expanded Disability Status Scale score, 2.0-5.0) and 12 age- and sex-matched controls. RESULTS: There were no differences in cycling time between diets in either group (P = .29). The MS group had no changes in fatigue between diets (P = .64); the control group demonstrated increased total mental fatigue after FAT (P = .05). The control group increased carbohydrate oxidation by 24% at rest and 13% during exercise after CARB. Similarly, the control group significantly increased fat oxidation after FAT by 22% at rest and 68% during exercise (P = .01). These changes were not seen in the MS group. Compared with controls, persons with MS oxidized approximately 50% less fat during exercise after FAT (P = .05). CONCLUSIONS: Neither CARB nor FAT altered submaximal exercise performance or baseline fatigue in the MS group. The results suggest that persons with MS are unable to adapt to dietary changes and oxidize fatty acids as efficiently as controls.

Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl-CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down-regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver-specific PDC-deficient mouse (L-PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L-PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscle-type 2, and lactate dehydrogenase B as well as those for the nonglycolysis-related proteins, CD-36, C/EBP homologous protein, and peroxisome proliferator-activated receptor γ, were up-regulated in L-PDCKO liver whereas hypoxia-induced factor-1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down-regulated. The protein levels of pyruvate kinase muscle-type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC-deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L-PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver-specific PDC deficiency is sufficient to induce "aerobic glycolysis characteristic" in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.

Excessive early-life cholesterol exposure may have later-life consequences for nonalcoholic fatty liver disease.

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Age and Sex Influence Mitochondria and Cardiac Health in Offspring Exposed to Maternal Glucolipotoxicity.

Infants of diabetic mothers are at risk of cardiomyopathy at birth and myocardial infarction in adulthood, but prevention is hindered because mechanisms remain unknown. We previously showed that maternal glucolipotoxicity increases the risk of cardiomyopathy and mortality in newborn rats through fuel-mediated mitochondrial dysfunction. Here we demonstrate ongoing cardiometabolic consequences by cross-fostering and following echocardiography, cardiomyocyte bioenergetics, mitochondria-mediated turnover, and cell death following metabolic stress in aged adults. Like humans, cardiac function improves by weaning with no apparent differences in early adulthood but declines again in aged diabetes-exposed offspring. This is preceded by impaired oxidative phosphorylation, exaggerated age-related increase in mitochondrial number, and higher oxygen consumption. Prenatally exposed male cardiomyocytes have more mitolysosomes indicating high baseline turnover; when exposed to metabolic stress, mitophagy cannot increase and cardiomyocytes have faster mitochondrial membrane potential loss and mitochondria-mediated cell death. Details highlight age- and sex-specific roles of mitochondria in developmentally programmed adult heart disease.

Maternal hypercholesterolemia programs dyslipidemia in adult male mouse progeny.

As a collection of metabolic abnormalities including inflammation, insulin resistance, hypertension, hormone imbalance, and dyslipidemia, maternal obesity has been well-documented to program disease risk in adult offspring. Although hypercholesterolemia is strongly associated with obesity, less work has examined the programming influence of maternal hypercholesterolemia (MHC) independent of maternal obesity or high-fat feeding. This study was conducted to characterize how MHC per se impacts lipid metabolism in offspring. Female (n = 6/group) C57BL/6J mice were randomly assigned to: (1.) a standard chow diet (Control, CON) or (2.) the CON diet supplemented with exogenous cholesterol (CH) (0.15%, w/w) throughout mating and the gestation and lactation periods. At weaning (postnatal day (PND) 21) and adulthood (PND 84), male offspring were characterized for blood lipid and lipoprotein profile and hepatic lipid endpoints, namely cholesterol and triglyceride (TG) accumulation, fatty acid profile, TG production, and mRNA expression of lipid-regulatory genes. Both newly weaned and adult offspring from CH mothers demonstrated increased very low-density lipoprotein (VLDL) particle number and size and hepatic TG and n-6 polyunsaturated fatty acid accumulation. Further, adult CH offspring exhibited reduced fatty acid synthase (Fasn) and increased diglyceride acyltransferase (Dgat1) mRNA expression. These programming effects appear to be independent of changes in hepatic TG production and postprandial lipid clearance. Study results suggest that MHC, independent of obesity or high-fat feeding, can induce early changes to serum VLDL distribution and hepatic lipid profile that persist into adulthood.

Evaluating the Lipid-Lowering Effects of α-lipoic Acid Supplementation: A Systematic Review.

Dietary supplementation of α-lipoic acid, an 8-carbon organosulfur compound, has been widely reported to lower blood glucose concentration and/or improve insulin sensitivity in previous randomized controlled trials. Although animal model studies further report fairly consistent lipid lowering in both blood and tissue pools in response to α-lipoic acid supplementation, results from human studies are mixed. According to PRISMA guidelines, we conducted a systematic review of published randomized controlled studies (RCTs) to assess the efficacy of α-lipoic acid supplementation as a strategy to improve dyslipidemia, with a focus on serum lipid endpoints including TC, low density lipoprotein cholesterol (LDL-C), HDL-C, and TG. PubMed, EMBASE, Cochrane Evidence-Based Medicine Reviews, Proquest, Web of Science, and Scopus were searched to identify RCTs that reported the effects of α-lipoic acid on blood lipid concentrations from 1970 to 2017. We included RCTs reporting blood lipid responses in adults supplemented with oral α-lipoic acid versus a placebo or control for at least one month. Studies were reviewed and data were extracted by two independent study authors. Seventeen studies were deemed eligible for inclusion. Overall, mean percent changes in blood lipid endpoints in response to α-lipoic acid varied considerably between studies for total cholesterol (-10.5 to +13.9), low-density lipoprotein cholesterol (-19.67 to +9.06), high-density lipoprotein cholesterol (-12.5 to +29.20), and triglycerides (-38.57 to +17.0). Results of this systematic review suggest little consistent benefit on serum lipids in response to α-lipoic acid supplementation. Further well-controlled studies designed and powered to detect improvements in blood lipids in hypercholesterolemic individuals are warranted (PROSPERO registration number: CRD42018105933).

Metabolic effects of α-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study.

Supplementation of health promoting nutraceuticals may be an effective adjunct strategy with other lifestyle and drug approaches to impede disease progression in prediabetic subjects. α-Lipoic acid, a naturally occurring short-chain fatty acid, has been extensively evaluated for its antioxidant and glycemic control properties but has rarely been investigated as a lipid-lowering strategy. We conducted a pilot study to examine the effects of α-lipoic acid supplementation on glycemic control and lipid profile in pre-diabetic, overweight/obese adults. The study was designed as a free-living, randomized, two-phase, placebo-controlled cross-over study with 12 pre-diabetic, dyslipidemic subjects. Eligible subjects completed two thirty-day phases (in random order) consisting of a placebo (600 mg cellulose per day) and α-lipoic acid treatment (600 mg day-1). Although no change (p < 0.05) in serum glucose was observed, α-lipoic acid-supplemented subjects demonstrated reduced fasting serum insulin (p = 0.04) and HOMA-IR (p = 0.07) compared with the placebo group. However, no change (p > 0.05) in serum lipids (including total cholesterol, LDL-C, HDL-C, triglycerides, LDL-C/HDL-C, and TC/HDL-C) were observed. Study results suggest that α-lipoic acid supplementation may be a useful strategy to improve insulin sensitivity in pre-diabetic subjects but is not effective in modulating serum lipids.