Effects of dietary fatty acids on burn-induced immunosuppression

Previous studies from our laboratory established that low-fat diets prevent immunosuppression and reduce oxidative stress after a thermal injury. The purpose of the present study was to test the hypothesis that the type of dietary fatty acid influences splenocyte proliferation and oxidative stress following a burn injury. Female C3H/HeN mice were fed ad libitum six experimental diets (5% w/w lipids) differing in fatty acid composition for 10 days following a burn injury. Compared to the controls, burned mice fed whichever diet showed lower lymphoproliferative responses to concanavalin-A (Con-A) and lipopolysaccharide (LPS) (p<0.01), but not to an anti-T cell receptor monoclonal antibody (H-57). In burned animals, nitric oxide (NO) concentration was negatively correlated to the proliferation induced by Con-A (p<0.01) or LPS (p<0.05). These results suggest that: (1) dietary fatty acid type does not influence the splenocyte proliferation or oxidative stress and (2) NO production is involved in the immunosuppression following burn injury.     

Effects of excess dietary iron and fat on glucose and lipid metabolism

PurposeDiets rich in fat and energy are associated with metabolic syndrome (MS). Increased body iron stores have been recognized as a feature of MS. High-fat diets (HFs), excess iron loading and MS are closely associated, but the mechanism linking them has not been clearly defined. We investigated the interaction between dietary fat and dietary Fe in the context of glucose and lipid metabolism in the body.MethodsC57BL6/J mice were divided into four groups and fed the modified AIN-93G low-fat diet (LF) and HF with adequate or excess Fe for 7 weeks. The Fe contents were increased by adding carbonyl iron (2% of diet weight) (LF+Fe and HF+Fe).ResultsHigh iron levels increased blood glucose levels but decreased high-density lipoprotein cholesterol levels. The HF group showed increases in plasma levels of glucose and insulin and insulin resistance. HF+Fe mice showed greater changes. Representative indices of iron status, such hepatic and plasma Fe levels, were not altered further by the HF. However, both the HF and excess iron loading changed the hepatic expression of hepcidin and ferroportin. The LF+Fe, HF and HF+Fe groups showed greater hepatic fat accumulation compared with the LF group. These changes were paralleled by alterations in the levels of enzymes related to hepatic gluconeogenesis and lipid synthesis, which could be due to increases in mitochondrial dysfunction and oxidative stress.ConclusionsHigh-fat diets and iron overload are associated with insulin resistance, modified hepatic lipid and iron metabolism and increased mitochondrial dysfunction and oxidative stress.     

Intentional Weight Loss Reduces Mortality Rate in a Rodent Model of Dietary Obesity

Objective: We used a rodent model of dietary obesity to evaluate effects of caloric restriction‐induced weight loss on mortality rate. Research Measures and Procedures: In a randomized parallel‐groups design, 312 outbred Sprague‐Dawley rats (one‐half males) were assigned at age 10 weeks to one of three diets: low fat (LF; 18.7% calories as fat) with caloric intake adjusted to maintain body weight 10% below that for ad libitum (AL)‐fed rat food, high fat (HF; 45% calories as fat) fed at the same level, or HF fed AL. At age 46 weeks, the lightest one‐third of the AL group was discarded to ensure a more obese group; the remaining animals were randomly assigned to one of three diets: HF‐AL, HF with energy restricted to produce body weights of animals restricted on the HF diet throughout life, or LF with energy restricted to produce the body weights of animals restricted on the LF diet throughout life. Life span, body weight, and leptin levels were measured. Results: Animals restricted throughout life lived the longest (p < 0.001). Life span was not different among animals that had been obese and then lost weight and animals that had been nonobese throughout life (p = 0.18). Animals that were obese and lost weight lived substantially longer than animals that remained obese throughout life (p = 0.002). Diet composition had no effect on life span (p = 0.52). Discussion: Weight loss after the onset of obesity during adulthood leads to a substantial increase in longevity in rats.     

Influence of dietary fat on some metabolic responses of cattle to hyperthermia induced by heat exposure

1. Two breeds of cattle which differ in their plasma concentrations of lipid components (PCLC) and ability to tolerate heat were used to study metabolic responses to hyperthermia. Two maintenance diets, LF (2.5% Fat) and HF (9.2% Fat), which were isonitrogenous and isocaloric were used. 2. The PCLC, the net esterification of cholesterol by the lecithin: cholesterol acyl transferase system and faecal fat excretion were increased by the HF diet which reduced urinary N loss. 3. Hyperthermia disturbed lipid metabolism in all animals and reductions in the concentrations of plasma cholesterol and phospholipid paralleled the increases in the quantities of fat excreted in the faeces. 4. Within breeds the animals on the HF diet maintained a higher PCLC, lower body temperature and conserved more body nitrogen during hyperthermia than animals on the LF diet. 5. The results point to a role for dietary lipid in ameliorating the metabolic disturbances in animals during chronic hyperthermia.     

A Murine Model of Obesity With Accelerated Atherosclerosis

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity‐accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E–deficient (apoE^?/?) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE^?/? mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute‐phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro‐ and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high‐density lipoprotein (HDL). Moreover, SAA was localized with apoB‐containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE‐deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.     

Effect of dietary polyunsaturated fat and 7,12-dimethylbenz(a)-anthracene on rat splenic natural killer cells and prostaglandin E synthesis

Summary Dietary polyunsaturated fat has been shown to stimulate mammary tumorigenesis induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA). Studies were undertaken to investigate the effect of polyunsaturated fat and DMBA on splenic natural killer (NK) activity and prostaglandin E (PGE) synthesis. In a first experiment, splenic NK activity at 33, 55, 75, and 110 days of age was measured in Sprague-Dawley rats fed 0.5% low fat (LF), 5% normal fat (NF), or 20% high fat (HF) corn oil diets from 23 days of age. At 55 days of age, half of the rats from the 75 and 110 day age groups were given 5 mg DMBA. Ten days after the initiation of the diets splenic NK activity against YAC-1 lymphoma was decreased from 50% cytotoxicity in rats fed NF diet to 21% cytotoxicity in rats fed HF diet, but was not affected by LF feeding. No difference in NK activity was observed among the groups at the later time periods. DMBA had no effect on NK activity at 20 or 55 days after its administration. In a second experiment, where DMBA (15 mg/rat) was given to half of the rats at 50 days of age and NF or HF diets were started 3 days later, NK activity was 35% in rats fed NF diet and 21% in rats fed HF diet, 5 days after the diets were started. No difference in NK activity in rats fed either diet was observed at later time periods. DMBA decreased both NK activity and spleen cellularity transiently. In both experiments, PGE synthesis by spleen cells cultured for 18 h was not affected by dietary fat intake, but was slightly increased 3 days after DMBA administration. Results from these experiments suggest that the stimulation of DMBA-induced mammary tumorigenesis by polyunsaturated fat and by DMBA itself may possibly be mediated by a transient decrease in splenic NK cell activity.This work was supported by grants CA-35641, CA-33240, CA-13038 and Core Grant CA-24538 from the National Cancer Institute     

Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells

In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages and on macrophage-mediated cytotoxicity towards L929 and P815 cells were investigated. C57Bl6 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the principal fat source. The fatty acid composition of the macrophages was markedly influenced by that of the diet fed. Lipopolysaccharide (LPS)-stimulated macrophages from FO-fed mice showed significantly lower production (up to 80%) of PGE2 than those from mice fed on each of the other diets. There was a significant positive linear correlation between the proportion of arachidonic acid in macrophage lipids and the ability of macrophages, to produce PGE2. Lipopolysaccharide-stimulated TNF-alpha production by macrophages decreased with increasing unsaturated fatty acid content of the diet (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed significantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macrophages from mice fed on the LF diet. Macrophages from FO-fed mice showed significantly higher production of nitrite than those from mice fed on the OO and SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO diets significantly decreased macrophage- mediated killing of P815 cells (killed by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compared with feeding the LF diet, feeding the OO or SO diets significantly decreased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oil or FO feeding did not alter killing of L929 cells by macrophages, compared with feeding the LF diet. It is concluded that the type of fat in the diet affects macrophage composition and alters the ability of macrophages to produce cytotoxic and immunoregulatory mediators and to kill target tumour cells.     

Burn-induced oxidative stress is altered by a low zinc status: kinetic study in burned rats fed a low zinc diet

As an initial subdeficient status of zinc, considered as an essential antioxidant trace element, is frequent in burned patients, we aim to assess the effects of low zinc dietary intakes on burn-induced oxidative stress, in an animal model. After 8 weeks of conditioning diets containing 80 ppm (control group) or 10 ppm of zinc (depleted group), Wistar rats were 20% TBSA burned and sampled 1-10 days after injury. Kinetic evolutions of zinc status, plasma oxidative stress parameters, and antioxidant enzymes were also studied in blood and organs. The zinc-depleted diet induced, before injury, a significant decrease in zinc bone level and the increase of oxidative stress markers without stimulation of antioxidant enzyme activity. After burn, more markedly in zinc depleted animals than in controls, zinc levels decreased in plasma and bone, while increasing in liver. The decrease of thiol groups and GSH/GSSG ratio and the depression of GPx activity in liver are also moderately emphasized. Nevertheless, depleted zinc status could not be considered as determining for oxidative damages after burn injury. Further investigations must also be done to enlighten the mechanism of beneficial effects of zinc supplementation reported in burned patients.     

Cholesterol-lowering action and antioxidative effects of microbial gum in C57BL/6N mice fed a high fat diet

The effect of feeding microbial gum on lipid metabolism and antioxidative status in high fat-fed C57BL/6N mice was investigated. The animals were randomly divided and fed with a normal control diet (NC group), a high fat diet (HF group), or a high fat diet supplemented with microbial gum (HFG group) for 7 weeks. At the end of the experimental period, the HF mice exhibited a marked increase in body weight, plasma and hepatic total cholesterol levels, and lipid peroxidation rate. Reduced activities of hepatic lipogenic and antioxidant enzymes were also observed in the HF group relative to that of the NC group. In contrast, feeding microbial gum counteracted the high fat diet-induced body weight gain, hypercholesterolemia, and oxidative stress by regulating antioxidant and lipogenic enzyme activities. These findings illustrate that microbial gum possess cholesterol-lowering action and antioxidant status-improving ability and may be useful for preventing and treating high fat diet-induced obesity and possibly reduce the risk of obesity-related diseases.     

High‐fat diet and hydrochlorothiazide increase oxidative stress in brain of rats

This study evaluated the effect of possible synergic interaction between high fat diet (HF) and hydrochlorothiazide (HCTZ) on biochemical parameters of oxidative stress in brain. Rats were fed for 16 weeks with a control diet or with an HF, both supplemented with different doses of HCTZ (0.4, 1.0, and 4.0 g kg⁻¹ of diet). HF associated with HCTZ caused a significant increase in lipid peroxidation and blood glucose levels. In addition, HF ingestion was associated with an increase in cerebral lipid peroxidation, vitamin C and non‐protein thiol groups (NPSH) levels. There was an increase in vitamin C as well as NPSH levels in HCTZ (1.0 and 4.0 g kg⁻¹ of diet) and HF plus HCTZ groups. Na⁺–K⁺‐ATPase activity of HCTZ (4.0 g kg⁻¹ of diet) and HCTZ plus HF‐fed animals was significantly inhibited. Our data indicate that chronic intake of a high dose of HCTZ (4 g kg⁻¹ of diet) or HF change biochemical indexes of oxidative stress in rat brain. Furthermore, high‐fat diets consumption and HCTZ treatment have interactive effects on brain, showing that a long‐term intake of high‐fat diets can aggravate the toxicity of HCTZ. Copyright © 2009 John Wiley & Sons, Ltd.     

Regional heterogeneity of functional changes in conduit arteries after high-fat diet

Objective: To determine effects of dietary fat content on vascular responses in different conduit arteries in mice. Methods and Procedures: Vascular responses to reactive oxygen species (ROS)/hydroxyl radical (·OH), acetylcholine (ACh), endothelin‐1 (ET‐1), and angiotensin II (Ang II) were determined in carotid and femoral arteries of C57BL/6J mice fed with diets varying in fat content (low fat (LF), 12.3%; high fat (HF), 41%; and very high fat (VHF), 58% (kcal from fat)) for 15 weeks, beginning at 4 weeks of age. Results: In precontracted rings of carotid and femoral artery, ROS/·OH‐induced a rapid, transient vasodilation. In the carotid, but not in femoral artery, ROS/·OH‐induced dilation increased with increasing dietary fat intake (P < 0.05 vs. LF diet), while contractile responses to ROS/·OH remained unaffected. In femoral arteries, ROS/·OH‐induced contractions were reversed into relaxations after both HF and VHF diet (P < 0.05 vs. LF diet). Both ET‐1 and Ang II induced strong contractions in the femoral artery that were unaffected by dietary fat intake. In contrast, in the carotid artery Ang II–induced contraction was attenuated after HF and VHF diets (P < 0.005 vs. LF diet), whereas ET‐1‐induced vasoconstriction was significantly increased (P < 0.05 VHF vs. LF and HF). Treatment with VHF diet enhanced ACh‐mediated endothelium‐dependent relaxation only in the femoral artery (P < 0.05 vs. HF). Discussion: These findings demonstrate that dietary fat content has regional and distinct effects on vascular function in different vascular beds. The data also suggest the possibility that in selected conduit arteries ROS‐dependent vasodilator mechanisms become activated in response to increased dietary fat intake.     

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.     

Moderate intake of BCAA-rich protein improves glucose homeostasis in high-fat-fed mice

Notwithstanding the fact that dietary branched-chain amino acids (BCAAs) have been considered to be a cause of insulin resistance (IR), evidence indicates that BCAA-rich whey proteins (WPs) do not lead to IR in animals consuming high-fat (HF) diets and may instead improve glucose homeostasis. To address the role of BCAA-rich WP as dietary protein in IR and inflammatory response, we fed C57BL/6J mice either high-fat (HF) or low-fat (LF) diets formulated with moderate protein levels (13% w/w) of either WP or hydrolyzed WP (WPH) and compared them with casein (CAS) as a reference. The muscle and plasma free amino acid profiles, inflammatory parameters and glycemic homeostasis were examined. While the LF/CAS diet promoted the rise in triglycerides and inflammatory parameters, the HF/CAS induced typical IR responses and impaired biochemical parameters. No differences in plasma BCAAs were detected, but the HF/WPH diet led to a twofold increase in gastrocnemius muscle free amino acids, including BCAAs. In general, ingestion of WPH was effective at averting or attenuating the damage caused by both the LF and HF diets. No high concentrations of BCAAs in the plasma or signs of IR were found in those mice fed an HF diet along with the hydrolyzed whey proteins. It is concluded that consumption of BCAA-rich whey proteins, especially WPH, does not result in the development of IR.     

Obesity induced by a high-fat diet downregulates apolipoprotein A-IV gene expression in rat hypothalamus

Apolipoprotein A-IV (apo A-IV) is an anorectic protein produced in the intestine and brain that has been proposed as a satiety signal. To determine whether diet-induced obesity alters apo A-IV gene expression in the intestine and hypothalamus, rats were fed a high-fat (HF), low-fat (LF), or standard chow (CHOW) diet for 2, 4, 6, 8, or 10 wk. Rats fed the HF diet had significantly greater body weights than rats given the LF and CHOW diets. Intestinal and plasma apo A-IV levels were comparable across dietary groups and time. LF and CHOW rats had comparable hypothalamic apo A-IV mRNA across the course of the experiment. However, HF rats had a slow and progressive diminution in hypothalamic apo A-IV mRNA over time that became significantly lower than that of LF or CHOW rats by 10 wk. Intragastric infusion of lipid emulsion to animals that were fasted overnight significantly stimulated hypothalamic apo A-IV mRNA in LF and CHOW rats but had no effect in HF rats. These results demonstrate that chronic consumption of a HF diet significantly reduces apo A-IV mRNA levels and the response of apo A-IV gene expression to dietary lipids in the hypothalamus. This raises the possibility that dysregulation of hypothalamic apo A-IV could contribute to diet-induced obesity.     

Meal-feeding studies in mice: effects of diet on blood lipids and energy expenditure

To identify optimal study-design conditions to investigate lipid metabolism, male, C57BL/6J mice (age, 59 +/- 3 days) were allotted to eight groups, with six animals per group that were stratified by three factors: diet type (high fat [HF]: 60% of energy from fat versus that of a standard rodent diet, 14% fat, fed for 7 weeks), feeding regimen (ad libitum [ad lib] versus meal fed), and metabolic state (data collected in fasted or fed states). Serum free fatty acids (FFA) and triacylglycerols (TAG) concentrations, and energy expenditure (EE) were assessed. Mice gained 0.30 +/- 0.11 g of body weight/day when allowed ad lib access to HF diet, similar weight when meal-fed the HF or ad lib-fed the standard diet (0.10 +/- 0.03 g/day), and no weight when meal-fed the standard diet (0.01 +/- 0.02 g/day). Fed-state TAG concentration was 88 to 100% higher (P < 0.02) than that of the fasted state, except when animals were ad lib-fed the HF diet. When the standard diet was meal fed, FFA concentration was 30% higher in the fasted compared with the fed state (P = 0.003). Mice had 33% higher postprandial EE when either diet was meal fed (P = 0.01). Mice adapted to meal feeding developed transitions in metabolism consistent with known physiologic changes that occur from fasting to feeding. When fed the standard diet, a 6-h per day meal-feeding regimen was restrictive for normal growth. These data support use of a meal-feeding regimen when HF diets are used and research is focused on metabolic differences between fasted and fed states. This protocol allows study of the metabolic effects of an HF diet without the confounding effects of over-consumption of food and excess body weight gain.     

Interactions of dietary fat and 2,5-anhydro-D-mannitol on energy metabolism in isolated rat hepatocytes

The fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding in rats by reducing ATP content in the liver. These behavioral and metabolic effects occur with rats fed a high-carbohydrate/low-fat (HC/LF) diet, but they are prevented or attenuated when the animals eat high-fat/low-carbohydrate (HF/LC) food. To examine the metabolic bases for this effect of diet, we assessed the actions of 2,5-AM on ATP content, oxygen consumption, and substrate oxidation in isolated hepatocytes from rats fed one of the two diets. Compared with cells from rats fed the HC/LF diet ("HC/LF" cells), cells from rats fed the HF/LC diet ("HF/LC" cells) had similar ATP contents but lower oxygen consumption, decreased fructose, and increased palmitate oxidation. 2,5-AM did not decrease ATP content or oxygen consumption in HF/LC cells as much as it did in HC/LF hepatocytes, and it only affected fructose and palmitate oxidation in HC/LF cells. 31P-NMR spectroscopy indicated that differences in phosphate trapping accounted for differences in depletion of ATP by 2,5-AM. These results suggest that intake of the HF/LC diet prevents the eating response and attenuates the decline in liver ATP by shifting hepatocyte metabolism to favor fat over carbohydrate as an energy-yielding substrate.     

A high-fat, ketogenic diet induces a unique metabolic state in mice

Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.     

Maternal obesogenic diet enhances cholestatic liver disease in offspring

Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventional chow (CON) or high fat/high sucrose (HF/HS) diet and then bred them with lean males. Offspring were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 2 weeks to induce cholestasis, and a subgroup was then fed CON for an additional 10 days. Additionally, to evaluate the role of the gut microbiome, we fed antibiotic-treated mice cecal contents from CON or HF/HS offspring, followed by DDC for 2 weeks. We found that HF/HS offspring fed DDC exhibited increased fine branching of the bile duct (ductular reaction) and fibrosis but did not differ in BA pool size or intrahepatic BA profile compared to offspring of mice fed CON. We also found that after 10 days recovery, HF/HS offspring exhibited sustained ductular reaction and periportal fibrosis, while lesions in CON offspring were resolved. In addition, cecal microbiome transplant from HF/HS offspring donors worsened ductular reaction, inflammation, and fibrosis in mice fed DDC. Finally, transfer of the microbiome from HF/HS offspring replicated the cholestatic liver injury phenotype. Taken together, we conclude that maternal HF/HS diet predisposes offspring to increased cholestatic injury after DDC feeding and delays recovery after returning to CON diets. These findings highlight the impact of maternal obesogenic diet on hepatobiliary injury and repair pathways during experimental cholestasis.     

The effect of dietary lipid content and stress on egg quality in farmed Atlantic cod Gadus morhua

The present study assessed differences in fecundity and egg quality from Atlantic cod Gadus morhua fed isoproteic diets containing 13% fat (low fat, LF) or 20% fat (high fat, HF) and either stressed or left unstressed as a control over the spawning season. Each diet was fed to triplicate groups of G. morhua from June 2009, through to first maturation and spawning. In January 2010 sub-groups of G. morhua were moved to land-based spawning tanks where the experimental trial was carried out. At the start of the experiment, G. morhua fed the high-fat diet were significantly larger than G. morhua fed low-fat diet. These differences were maintained through the spawning season, although with a loss of mass in both dietary groups. Relative fecundity through the season was significantly lower in stressed G. morhua fed LF compared to unstressed G. morhua fed the same diet. Stressed G. morhua had a higher variability in weekly amount of eggs spawned, spawning occurred more irregularly, and the spawning period lasted longer than in unstressed G. morhua. Several egg quality variables were also affected: eggs from G. morhua fed LF and exposed to stress had lower fertilization and hatching rates compared to the unstressed G. morhua fed the same diet as well as all G. morhua fed HF. Gadus morhua fed a low-fat diet appeared less tolerant to stress than fish fed a high-fat diet.     

Metabolic Implications of Dietary Trans‐fatty Acids

Dietary trans‐fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high‐fat saturated diets, relative to low‐fat diets, induce adiposity and whole‐body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low‐fat diet containing elaidic acid (18:1t), the predominant trans‐fatty acid isomer found in the human food supply. Male 8‐week‐old Sprague–Dawley rats were fed a 10% trans‐fatty acid enriched (LF‐trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (¹H‐MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic–hyperinsulinemic clamps (week 8) determined whole‐body and tissue‐specific insulin sensitivity followed by high‐resolution ex vivo ¹H‐NMR to assess tissue biochemistry. Rats fed the LF‐trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low‐fat control diet. Net glycogen synthesis was also increased in the LF‐trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF‐trans diet, whereas in rats fed a 45% saturated fat (HF‐sat) diet, impaired glucose disposal corresponded to increased IMCL_TA. Neither diet induced an increase in IMCL_soleus. These findings imply that trans‐fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans‐fatty acids induce insulin resistance differs from diets enriched with saturated fats.