Heterozygous midnolin knockout attenuates severity of nonalcoholic fatty liver disease in mice fed a Western-style diet high in fat, cholesterol, and fructose.

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first functional global midnolin knockout mouse model. Although the overwhelming majority of global homozygous midnolin knockout mice demonstrated embryonic lethality, heterozygous knockout mice were observed to be similar to wild-type mice in their viability and were used to determine the effect of reduced midnolin expression on NAFLD. We found that global heterozygous midnolin knockout attenuated the severity of NAFLD in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism. Collectively, our results support a role for midnolin in regulating cholesterol/lipid metabolism in the liver. Thus, midnolin may represent a novel therapeutic target for NAFLD. Finally, our observation that midnolin was essential for survival underscores the broad importance of this gene beyond its role in liver biology.NEW & NOTEWORTHY We have developed and now report on the first functional global midnolin knockout mouse model. We found that global heterozygous midnolin knockout attenuated the severity of nonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.

Dietary cholesterol drives the development of nonalcoholic steatohepatitis by altering gut microbiota mediated bile acid metabolism in high-fat diet fed mice.

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter ß) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.

Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fibrosis that develops from fatty liver. Disruption of intestinal microbiota homeostasis, dysbiosis, is associated with fibrosis development in NASH. An antimicrobial peptide α-defensin secreted by Paneth cells in the small intestine is known to regulate composition of the intestinal microbiota. However, involvement of α-defensin in NASH remains unknown. Here, we show that in diet-induced NASH model mice, decrease of fecal α-defensin along with dysbiosis occurs before NASH onset. When α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration or by oral administration of α-defensins, liver fibrosis is ameliorated with dissolving dysbiosis. Furthermore, R-Spondin1 and α-defensin improved liver pathologies together with different features in the intestinal microbiota. These results indicate that decreased α-defensin secretion induces liver fibrosis through dysbiosis, further suggesting Paneth cell α-defensin as a potential therapeutic target for NASH.

Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet.

Sugar consumption can readily lead to obesity and metabolic diseases such as liver steatosis. We previously demonstrated that a novel hypothalamic neuropeptide, neurosecretory protein GL (NPGL), promotes fat accumulation due to the ingestion of sugar by rats. However, differences in lipogenic efficiency of sugar types by NPGL remain unclear. The present study aimed to elucidate the obesogenic effects of NPGL on mice fed different sugars (i.e., sucrose or fructose). We overexpressed the NPGL-precursor gene (Npgl) in the hypothalamus of mice fed a medium-fat/medium-sucrose diet (MFSD) or a medium-fat/medium-fructose diet (MFFD). Food intake and body mass were measured for 28 days. Body composition and mRNA expression of lipid metabolic factors were measured at the endpoint. Npgl overexpression potently increased body mass with fat accumulation in the white adipose tissue of mice fed MFFD, although it did not markedly affect food intake. In contrast, we observed profound fat deposition in the livers of mice fed MFFD but not MFSD. In the liver, the mRNA expression of glucose and lipid metabolic factors was affected in mice fed MFFD. Hence, NPGL induced liver steatosis in mice fed a fructose-rich diet.

Heat-Inactivated Akkermansia muciniphila Improves Gut Permeability but Does Not Prevent Development of Non-Alcoholic Steatohepatitis in Diet-Induced Obese Ldlr-/-.Leiden Mice.

The development of non-alcoholic steatohepatitis (NASH) has been associated with alterations in gut microbiota composition and reduced gut barrier function. Akkermansia muciniphila is a gut microbe that is thought to have health-promoting properties, including the ability to improve gut barrier function and host metabolism, both when administered live and after heat-inactivation. We questioned whether heat-inactivated A. muciniphila may reduce NASH development. Ldlr-/-.Leiden mice, a translational, diet-induced model for NASH, were fed a NASH-inducing high-fat diet (HFD) supplemented with heat-inactivated A. muciniphila. After 28 weeks, effects of the treatment on obesity and associated metabolic dysfunction in the gut (microbiota composition and permeability), adipose tissue, and liver were studied relative to an untreated HFD control. Treatment with heat-inactivated A. muciniphila did not affect body weight or adiposity and had no effect on plasma lipids, blood glucose, or plasma insulin. Heat-inactivated A. muciniphila had some minor effects on mucosal microbiota composition in ileum and colon and improved gut barrier function, as assessed by an in vivo functional gut permeability test. Epidydimal white adipose tissue (WAT) hypertrophy and inflammation were not affected, but heat-inactivated A. muciniphila did reduce hypertrophy in the mesenteric WAT which is in close proximity to the intestine. Heat-inactivated A. muciniphila did not affect the development of NASH or associated fibrosis in the liver and did not affect circulating bile acids or markers of liver fibrosis, but did reduce PRO-C4, a type IV collagen synthesis marker, which may be associated with gut integrity. In conclusion, despite beneficial effects in the gut and mesenteric adipose tissue, heat-inactivated A. muciniphila did not affect the development of NASH and fibrosis in a chronic disease setting that mimics clinically relevant disease stages.

The effect of nutritional status on the pharmacokinetic profile of acetaminophen.

Nutritional imbalance (low protein / high fat) is a public health problem affecting many people in developing and developed nations. Such an imbalance will influence pathophysiological homeostasis in individuals and thereby considerably impact drug pharmacokinetics. It was reported that short-term fasting increases acetaminophen exposure in healthy subjects, whereas no effect was observed after a high-fat diet. These findings suggest the necessity of considering nutritional status when assessing the risk of acetaminophen-induced hepatotoxicity. Additionally, the role of nutrition status on the pharmacokinetic profile of acetaminophen (APAP) at toxic doses is either scanty or not available. With this background, we aimed to compare the effects of nutrition status on the pharmacokinetic profile of APAP at a toxic dose in three different dietary regimens like - Normal diet (ND), Low protein diet (LPD), and High-fat diet (HFD). Balb/C female mice were divided into three groups after weaning, and for the next 15 weeks, they were fed with their respective diets (ND, LPD, and HFD). After that, mice were dosed with APAP (300 mg/kg p.o), and blood sampling was done at different time intervals and centrifuged at 3000 rpm for 5 min to collect plasma samples. Plasma samples were analyzed using the HPLC method. Data analysis was done by Non-compartment analysis using Phoenix WinNonlin 8.3 software. LPD group shows higher values of Cmax, tmax, t1/2, and AUC0-4, AUC0-x values than ND and HFD groups. Both Cmax and AUC follow the pattern of drug exposure where LPD > ND > HFD. In conclusion, nutrition in the diet alters APAP pharmacokinetic profile at a toxic dose in three different diet regimes. Further study on CYP450 concentration and activity is essential to understand the pharmacokinetics difference between these dietary regimens.

Whole life exposure to low dose cadmium alters diet-induced NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a major global public health concern affecting more than 25% of the world's population. Although obesity and diabetes are major risk factors for NAFLD, they cannot account for all cases, indicating the importance of other factors such as environmental exposures. Cadmium (Cd) exposure is implicated in the development of NAFLD; however, the influence of early life, in utero Cd exposure on the development of diet-induced NAFLD is poorly understood. Therefore, we developed an in vivo, multiple-hit model to study the effect of whole-life, low dose Cd exposure on high fat diet (HFD)-induced NAFLD. Adult male and female C57BL/6 J mice fed normal diets (ND) were exposed to 0, 0.5 or 5 ppm Cd-containing drinking water for 14 weeks before breeding. At weaning, offspring were fed ND or HFD and continued on the same drinking water regimen as their parents for 24 weeks. Cd exposure at different concentrations differentially altered HFD-associated adverse health effects, including liver injury. HFD-induced increased body weight, decreased glucose tolerance. Liver injury and lipid deposition were exacerbated by 5 ppm Cd exposure but attenuated by 0.5 ppm Cd exposure. Further, HFD blunted the response of metallothionein, a major Cd detoxification protein, in mice exposed to 5 ppm Cd but enhanced the response in mice exposed to 0.5 ppm Cd, suggesting a possible mechanism for Cd alteration of HFD-induced NAFLD. These results confirm the multi-hit nature of NAFLD and show whole life, low dose Cd exposure alters HFD-induced NAFLD with outcomes dependent on Cd concentration.

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction.

BACKGROUND: Obesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI. METHODS: Male C57BL/6 mice were fed a HFD for eight weeks and then divided into Sham (Sham-operated) and +BAT (mice receiving 0.1 g BAT into their visceral cavity). Sixteen weeks post-transplantation, mice were further subdivided into ±MI (Sham; Sham-MI; +BAT; +BAT-MI) and maintained on a HFD. Cardiac (echocardiography) and metabolic function (glucose and insulin tolerance tests, body composition and exercise tolerance) were assessed throughout 22 weeks post-MI. Quantitative PCR (qPCR) was performed to determine the expression of genes related to metabolic function of perigonadal adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), liver, heart, tibialis anterior skeletal muscle (TA); and BAT. RESULTS: +BAT prevented the increase in left ventricle mass (LVM) and exercise intolerance in response to MI. Similar to what is observed in humans, Sham-MI mice developed IGT post-MI, but this was negated in +BAT-MI mice. IGT was independent of changes in body composition. Genes involved in inflammation, insulin resistance, and metabolism were significantly altered in pgWAT, scWAT, and liver in Sham-MI mice compared to all other groups. CONCLUSIONS: BAT transplantation prevents IGT, the increase in LVM, and exercise intolerance following MI. MI alters the expression of several metabolic-related genes in WAT and liver in Sham-MI mice, suggesting that these tissues may contribute to the impaired metabolic response. Increasing BAT may be an important intervention to prevent the development of IGT or T2D and cardiac remodeling in obese patients post-MI.

Combination of TRP channel dietary agonists induces energy expending and glucose utilizing phenotype in HFD-fed mice.

BACKGROUND: Bioactive dietary constituents activating Transient receptor potential (TRP) channels have emerged as promising candidates for the prevention of metabolic disorders. OBJECTIVE: The present study is an attempt to evaluate anti-obesity potential of a dietary TRP-based tri-agonist, combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist), and cinnamaldehyde (TRPA1 agonist) in high-fat diet (HFD)-fed mice. DESIGN: Male C57BL/6 J mice divided into three groups (n = 8), were fed on normal pellet diet (NPD), or high-fat diet (HFD) (60% energy by fat) and HFD + CB (combination of capsaicin 0.4 mg/Kg, menthol 20 mg/Kg, and cinnamaldehyde 2 mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied. RESULTS: Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis, and adipose tissue hypertrophy. Tri-agonist supplementation was found to induce browning of white adipose tissue and promote brown adipose tissue activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with a tri-agonist. CONCLUSION: The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.

Effect of a high-fat diet and chromium on hormones level and Cr retention in rats.

AIMS: The aim of the study was to determine how the administration of a high-fat diet supplemented with various forms of chromium to rats affects accumulation of this element in the tissues and levels of leptin, ghrelin, insulin, glucagon, serotonin, noradrenaline and histamine, as well as selected mineral elements. METHODS: The experiment was conducted on 56 male Wistar rats, which were divided into 8 experimental groups. The rats received standard diet or high fat diet (HFD) with addition of 0.3 mg/kg body weight of chromium(III) picolinate (Cr-Pic), chromium(III)-methioninate (Cr-Met), or chromium nanoparticles (Cr-NP). RESULTS: Chromium in organic forms was found to be better retained in the body of rats than Cr in nanoparticles form. However, Cr-Pic was the only form that increased the insulin level, which indicates its beneficial effect on carbohydrate metabolism. In blood plasma of rats fed a high-fat diet noted an increased level of serotonin and a reduced level of noradrenaline. The addition of Cr to the diet, irrespective of its form, also increased the serotonin level, which should be considered a beneficial effect. Rats fed a high-fat diet had an unfavourable reduction in the plasma concentrations of Ca, P, Mg and Zn. The reduction of P in the plasma induced by supplementation with Cr in the form of Cr-Pic or Cr-NP may exacerbate the adverse effect of a high-fat diet on the level of this element. CONCLUSION: A high-fat diet was shown to negatively affect the level of hormones regulating carbohydrate metabolism (increasing leptin levels and decreasing levels of ghrelin and insulin).

The Effects of Chronic Consumption of Lipid-Rich and Delipidated Bovine Dairy Milk on Brown Adipose Tissue Volume in Wild-Type Mice.

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. The ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of the MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high-fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, their body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in the BAT volume and mice consuming an HF diet in conjunction with FC BDM had a significantly greater BAT volume than all the other groups. Conversely, mice consuming an HF diet in addition to skim milk had a lower BAT volume compared to the HF control. The data presented suggest that the consumption of a high calorie diet in conjunction with FC BDM increases the BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors, including diet.

APOE ɛ4 Is Associated with Postprandial Inflammation in Older Adults with Metabolic Syndrome Traits.

The apolipoprotein E (APOE) polymorphism impacts blood lipids and biomarkers of oxidation and inflammation, contributing to an isoform-dependent disease risk. We investigated the effect of the APOE genotype on postprandial metabolism after consumption of three different isoenergetic (4200 kJ) meals in older adults with a CVD risk phenotype. In a randomized crossover study, participants with metabolic syndrome traits (APOE E3, n = 39; E4, n = 10; mean age, 70 ± 5 years; BMI 31.3 ± 3.0 kg/m2) consumed a Western-like diet high-fat (WDHF), Western-like diet high-carbohydrate (WDHC), or Mediterranean-like diet (MED) meal. Parameters of lipid and glucose metabolism, inflammatory, and oxidative parameters were analyzed in blood samples collected at fasting and 1-5 h postprandially. Data were analyzed by linear mixed models. The magnitude of the IL-6 increase after the WDHF meal was significantly higher in E4 than in E3 carriers (iAUC: E4 = 7.76 vs. E3 = 2.81 pg/mL × h). The time to detect the IL-6 increase was shorter in the E4 group. All meals produced postprandial glycemia, insulinemia, and lipidemia, without differences between the E3 and the E4 groups. IL-1ß and oxidized LDL levels did not change postprandially. In conclusion, APOE E4 carriers display increased postprandial inflammation, indicated by higher postprandial IL-6 increase, when compared to non-carriers.

Moringa, Rosemary and Purslane Leaves Extracts Alleviate Metabolic Syndrome in Rats Induced by High Fat-High Fructose Diet.

<b>Background and Objective:</b> Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance and dyslipidemia. This study aimed to investigate the impact of moringa, rosemary and purslane leave water extracts on metabolic syndrome in rats. <b>Materials and Methods:</b> Phenolic compounds in the plant leaves water extracts were determined by HPLC. Fifty adult male albino rats Sprague-Dawley strain were equally divided into five groups, group (1) Normal rats fed on the balanced diet, group (2) Metabolic syndrome rats fed on High Fat-High Fructose Diet (HF-HFD). The other three groups were fed on HF-HFD and orally administered 200 mg kg¹ b.wt. daily of the tested plant's leaves water extracts, respectively, for 12 weeks. Some anthropometric measurements (BMI, Lee index and adiposity index), biochemical parameters such as glucose hemostasis parameters (glucose, Insulin, HOMA-IR and GLP-1), lipids profile (TAGs, TC, LDL-C, HDL-C, free fatty acids, Apo-B and Apo A1), adipokines (leptin and adiponectin), some inflammatory markers (TNF-α and IL-6) and oxidative stress markers (PCC, NO and MDA), some anti-oxidant markers (GSH, CAT and TAOC) as well as, the gene expression level of endothelial nitric oxide synthase were determined. <b>Results:</b> The results revealed that feeding rats with HF-HFD for 12 weeks significantly increased anthropometric measurements, some inflammatory markers and oxidative stress markers and worsen glucose hemostasis parameters, lipids profile, adipokines and endothelial function as compared to the normal group. Moreover, co-administration of the tested plant's extracts at the tested dose to HF-HFD fed rats reduced the development of indicators of metabolic syndrome when compared to the metabolic syndrome group. <b>Conclusion:</b> The administered plant leaves water extracts at the tested dose could improve the features of metabolic syndrome. Rosemary leaves water extract has more effect in comparison with the other extracts.

The effects of dietary saturated fat source on weight gain and adiposity are influenced by both sex and total dietary lipid intake in zebrafish.

The effects of saturated fat intake on obesity and cardiovascular health remain inconclusive, likely due in part to their varied nature and interactions with other nutrients. Investigating the synergistic effects of different saturated fat sources with other dietary lipid components will help establish more accurate nutritional guidelines for dietary fat intake. Over the past two decades, zebrafish (Danio rerio) have been established as an attractive model system to address questions regarding contributions of dietary lipid intake to diet-induced obesity in humans. The goal of the present study was to assess interactions of three different saturated fat sources (milk fat, palm oil, and coconut oil) with sex and total dietary lipid intake on weight gain and body composition in adult zebrafish. Larvae were raised on live feeds until 28 days post fertilization, and then fed a formulated maintenance diet until three months of age. An eight-week feeding trial was then initiated, in which zebrafish were fed nine experimental low- and high-fat diets varying in saturated fatty acid and long-chain polyunsaturated fatty acid content, in addition to a low-fat and high-fat control diet. At termination of the feeding trial, each treatment was evaluated according to body mass, moisture content, and adiposity. Sex and diet significantly interacted in their effects on body mass (P = 0.026), moisture content (P = 0.044), and adiposity (P = 0.035). The influence of saturated fat source on body mass was observed to be dependent on intake of total dietary lipid. In females, all three saturated fat sources had similar effects on adiposity. From these observations, we hypothesize that impacts of saturated fat intake on energy allocation and obesity-related phenotypes are influenced by both sex and intake of other dietary lipid components. Our results suggest that current nutritional guidelines for saturated fat intake may need to be re-evaluated and take sex-specific recommendations into consideration.

Maternal DHA Supplementation during Pregnancy and Lactation in the Rat Protects the Offspring against High-Calorie Diet-Induced Hepatic Steatosis.

Maternal supplementation during pregnancy with docosahexaenoic acid (DHA) is internationally recommended to avoid postpartum maternal depression in the mother and improve cognitive and neurological outcomes in the offspring. This study was aimed at determining whether this nutritional intervention, in the rat, protects the offspring against the development of obesity and its associated metabolic disorders. Pregnant Wistar rats received an extract of fish oil enriched in DHA or saline (SAL) as placebo by mouth from the beginning of gestation to the end of lactation. At weaning, pups were fed standard chow or a free-choice, high-fat, high-sugar (fc-HFHS) diet. Compared to animals fed standard chow, rats exposed to the fc-HFHS diet exhibited increased body weight, liver weight, body fat and leptin in serum independently of saline or DHA maternal supplementation. Nevertheless, maternal DHA supplementation prevented both the glucose intolerance and the rise in serum insulin resulting from consumption of the fc-HFHS diet. In addition, animals from the DHA-fc-HFHS diet group showed decreased hepatic triglyceride accumulation compared to SAL-fc-HFHS rats. The beneficial effects on glucose homeostasis declined with age in male rats. Yet, the preventive action against hepatic steatosis was still present in 6-month-old animals of both sexes and was associated with decreased hepatic expression of lipogenic genes. The results of the present work show that maternal DHA supplementation during pregnancy programs a healthy phenotype into the offspring that was protective against the deleterious effects of an obesogenic diet.

Structural Studies of Water-Insoluble ß-Glucan from Oat Bran and Its Effect on Improving Lipid Metabolism in Mice Fed High-Fat Diet.

Water-insoluble ß-glucan has been reported to have beneficial effects on human health. However, no studies have thoroughly characterized the structure and function of water-insoluble ß-glucan in oat bran. Thus, the structure and effect of water-insoluble ß-glucan on weight gain and lipid metabolism in high-fat diet (HFD)-fed mice were analyzed. First, water-insoluble ß-glucan was isolated and purified from oat bran. Compared with water-soluble ß-glucan, water-insoluble ß-glucan had higher DP3:DP4 molar ratio (2.12 and 1.67, respectively) and molecular weight (123,800 and 119,200 g/mol, respectively). Notably, water-insoluble ß-glucan exhibited more fibrous sheet-like structure and greater swelling power than water-soluble ß-glucan. Animal experiments have shown that oral administration of water-insoluble ß-glucan tended to lower the final body weight of obese mice after 10 weeks treatment. In addition, water-insoluble ß-glucan administration significantly improved the serum lipid profile (triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels) and epididymal adipocytes size. What is more, water-insoluble ß-glucan reduced the accumulation and accelerated the decomposition of lipid in liver. In conclusion, water-insoluble ß-glucan (oat bran) could alleviate obesity in HFD-fed mice by improving blood lipid level and accelerating the decomposition of lipid.

Differences in the Concentration of Vitamin D Metabolites in Plasma Due to the Low-Carbohydrate-High-Fat Diet and the Eastern European Diet-A Pilot Study.

Vitamin D deficiency is a global problem with many health consequences, and it is currently recommended to supplement vitamin D. Change of diet should also be considered to ensure adequate vitamin D in the human body. The aim of this study was to assess the concentration of vitamin D metabolites in two different groups: one group on the low-carbohydrate-high-fat (LCHF) diet and the other group on the Eastern European (EE) diet. In the first stage, 817 participants declaring traditional EE diet or LCHF diet were investigated. Nutrition (self-reported 3-day estimated food record) and basic anthropometric parameters were assessed. After extra screening, 67 participants on the EE diet and 41 on the LCHF diet were qualified for the second stage. Plasma 25-hydroxycholecalciferol (25(OH)D3) and (25(OH)D2) concentration was measured by the validated HPLC-MS/MS method. Plasma 25(OH)D3 concentration was significantly higher in the group on the LCHF diet (34.9 ± 15.9 ng/mL) than in the group on the EE diet (22.6 ± 12.1 ng/mL). No statistical differences were observed in plasma 25(OH)D2 concentration between the study groups (p > 0.05). Women had a higher plasma 25(OH)D2 concentration than men regardless of diet type. The LCHF diet had a positive influence on plasma vitamin D concentration. However, long-term use of the LCHF diet remains contentious due to the high risk of cardiovascular disease. This study confirmed that the type of diet influences the concentration of vitamin D metabolites in the plasma.

Disruption of lateral hypothalamic calorie detection by a free choice high fat diet.

During the last few decades, the consumption of low-calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low-calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two-photon calcium imaging, we investigated how drinking sucrose or sucralose (a low-calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free-choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free-choice high fat diet shifts the glutamatergic neuronal response from sucrose-specific to sucralose-specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.