Liver Lipid Content Research Articles

Association of Visceral Fat and Liver Fat, Not Thigh Muscle Area nor Attenuation, with the Incidence of Type 2 Diabetes

Visceral fat, liver, and skeletal muscle are all major target organs of insulin and play key roles in the pathophysiology of type 2 diabetes. Not known is whether visceral fat, liver fat, and thigh skeletal muscle area or fat directly measured by computed tomography (CT) are independently associated with the incidence of type 2 diabetes. In a prospective cohort study, 1228 nondiabetic Japanese men and women were included. Intra-abdominal fat area (IAFA), liver-to-spleen (L/S) attenuation ratio to assess liver fat, and mid-thigh muscle area and attenuation were measured by CT. Low CT attenuation of liver and muscle reflects greater liver and intramuscular lipid content. Insulin resistance was assessed by HOMA-IR. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Discrete-time logistic hazard model was used. During the 7686 person-years of follow-up (median follow-up period, 7 years), 95 subjects developed type 2 diabetes. IAFA and L/S ratio, not thigh muscle area, were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included IAFA, L/S ratio, thigh muscle area, age, gender, family history of diabetes, HOMA-IR, smoking habit, daily alcohol consumption, and regular physical activity, odds ratios of type 2 diabetes for tertile 2 and 3 of IAFA were 2.23 (95% CI, 0.94-5.31) and 3.16 (1.33-7.52), respectively, compared to tertile 1, and those for tertile 1 and 2 of L/S ratio were 2.01 (1.01-3.97) and 2.(1.04-4.08), respectively, compared to tertile 3. However, those of tertile 2 and 3 of thigh muscle area were 0.76 (0.32-1.78) and 0.64 (0.24-1.69), respectively, compared to tertile 1. When thigh muscle attenuation was substituted for its area, results was identical to the above model. In conclusion, both greater amounts of visceral and liver fat, not thigh muscle area nor attenuation, were independently associated with the risk of type 2 diabetes. Disclosure K. Sato: None. S. Uehara: None. M. Shibata: None. Y. Hikita: None. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None.

Terminalia Sericea aqueous leaf extract protects growing wistar rats against fructose-induced fatty liver disease.

Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study interrogated the effects of T. sericea on linear growth, development of fatty liver disease, viscera morphometry and health of growing rats fed a 12% fructose solution (FS). Methods Thirty 21-day old male Wistar rat pups were randomly allocated to five treatments: group I - plain gelatine cubes (PGC) + plain tap water (PW), group II - 12% FS + PGC, group III - gelatine cubes containing fenofibrate (Feno) at a dose of 100 mg/kg body + FS, group IV - gelatine cubes containing the low dose (100 mg/kg body mass per day) of the T. sericea extract (TsL) + FS, group V - gelatine cubes containing the high dose (400 mg/kg body mass per day) of the T. sericea extract (TsH) + FS. Following 12 weeks of feeding, the rats were fasted overnight, euthanized and plasma and viscera harvested for analysis. Results Consumption of fructose resulted in significantly increased (p<0.05) liver lipid content and caused macrovesicular steatosis. The T. sericea extracts at 400 mg/kg per day suppressed the fructose-induced liver lipid accumulation and macrovesicular steatosis similarly to 100 mg/kg per day of Feno. Conclusions These findings suggest that the aqueous T. sericea leaf extract at 400 mg/kg per day could potentially protect against fructose-induced lipid accumulation as well as macrovesicular steatosis.

Effects of dietary lipid sources on growth performance, fatty acid composition and hepatic lipid metabolism of juvenile blunt snout bream, Megalobrama amblycephala

This study investigated the effects of dietary lipid sources on juvenile blunt snout bream, Megalobrama amblycephala. Juvenile blunt snout bream (14.40 ± 0.01 g) were fed diets containing 75 g/kg of fish oil (FO), linseed oil (LO), soybean oil, coconut oil (CO), rapeseed oil or beef tallow (BT) for 9 weeks. Survival rates, final weight, weight gain, feed efficiency ratio and feed intake remained unchanged. Viscerosomatic ratio, hepatosomatic index and condition factor were highest in fish fed the CO diet (p < 0.05). Whole‐body lipid content decreased, whereas liver lipid content increased in fish fed CO and BT diets (p < 0.05). Eicosapentaenoic acid and docosahexaenoic acid in the muscle and liver increased in fish fed the FO and LO diets (p < 0.05). FO and LO diets increased plasma glucose (p < 0.05). Feeding CO diet increased hepatic fatty acid synthase (FAS) and acetyl‐CoA carboxylase expression, and FAS activity (p < 0.05). Both CO and BT diets increased hepatic carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II expression, and CPT I activity compared to the FO diet (p < 0.05). These results indicate that LO can be substituted for FO in juvenile blunt snout bream diets without negative effects.

Polycyclic aromatic hydrocarbon exposure impairs pre-migratory fuelling in captively-dosed Sanderling (Calidris alba)

Efficient fuelling is essential for migratory birds because fuel loads and fuelling rates affect individual fitness and survival during migration. Many migrant shorebirds are exposed to oil pollution and its toxic constituents, polycyclic aromatic hydrocarbons (PAHs), at migratory staging sites, which has the potential to interfere with avian refuelling physiology. In this study, we orally dosed shorebirds with environmentally-relevant PAH mixtures to simulate dietary exposure during staging. Forty-nine wild-caught Sanderling (Calidris alba) were exposed to 0 (control), 12.6 (low), 126 (medium), or 1260 (high) μg total PAH/kg body weight/day. Birds were dosed during a 21-day period of autumn pre-migratory fuelling to mimic the typical staging duration of Sanderling. We measured daily changes in mass and fat loads, as well as ethoxyresorufin-O-deethylase (EROD) activity, serum biochemical profiles, and liver mass and lipid content following dosing. All dose groups gained fat and increased in mass (size-corrected) during the study period, with females having a higher average body mass than males. However, mass gain was 3.9, 5.4, and 3.8 times lower in the low, medium, and high dose groups, respectively, relative to controls, and body mass in the medium and high dose groups significantly declined near the end of the experiment. EROD activity showed a dose-dependent increase and was significantly elevated in the high dose group relative to controls. Higher individual EROD activity was associated with reduced serum bile acid and elevated serum creatine kinase concentrations in both sexes, and with elevated serum lipase concentrations in females. These results suggest that PAH exposure in Sanderling can interfere with mechanisms of lipid transport and metabolism, can cause muscle damage, and can lead to reduced overall fat loads that are critical to staging duration, departure decisions, migratory speed, and flight range. Given that many shorebirds migrate thousands of kilometers between the breeding and wintering grounds and frequently aggregate at key staging sites that are subject to contamination, PAH exposure likely represents a significant threat to shorebird migratory success.

Performance, egg quality, and liver lipid reserves of free-range laying hens naturally infected with Ascaridia galli.

A study was conducted to determine the performance, egg quality, and liver lipid reserves of laying hens exposed to ranges contaminated with Ascaridia galli. Sixteen-week-old Lohmann Brown laying hens (n = 200) were divided into 4 treatments with 5 replicates containing 10 hens per pen. Hens of treatment 1 [negative control (NC)] ranged on a decontaminated area, and hens of treatments 2 (low infection) and 3 (medium infection) ranged on areas previously contaminated by hens artificially infected with 250 and 1,000 embryonated A. galli eggs, respectively. The hens of treatment 4 [positive control (PC)] ranged on areas previously contaminated by hens artificially infected with 2,500 embryonated A. galli eggs, and in addition these hens were orally inoculated with 1,000 embryonated eggs. Results indicated that hens of the medium infection group had a higher number of intestinal A. galli worms and A. galli eggs in the coprodeum excreta (43.9 ± 4.0 and 3,437± 459 eggs/g) compared to hens of the low infection group (23.8 ± 4.0 and 1,820± 450 eggs/g) (P < 0.01) and similar worm counts to PC hens (34.4 ± 4.0 and 2,918± 474) (P>0.05). Egg production, egg mass, feed intake, and feed conversion ratio (FCR) were not affected by A. galli infection (P > 0.05). Egg quality parameters (egg weight, shell reflectivity, shell weight, shell thickness, shell percentage, shell breaking strength, deformation, albumen height, Haugh unit, and yolk score) were not affected by A. galli infection (P > 0.05). Highly infected hens had lower liver lipid content (2.72± 0.51g) compared to uninfected hens (4.46± 0.58g, P < 0.01). The results indicate that exposure to ranges contaminated with A. galli resulted in infection of the ranging hens, but this did not affect egg production or egg quality. Infection with A. galli lowered the liver lipid reserves of the host significantly, suggesting infected hens use more energy reserves for maintenance and production.

Neonatal intake of oleanolic acid attenuates the subsequent development of high fructose diet-induced non-alcoholic fatty liver disease in rats.

Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47-49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.

A Long-term Estrogen Deficiency in Ovariectomized Mice is Associated with Disturbances in Fatty Acid Oxidation and Oxidative Stress.

The aim of this work was to evaluate the changes caused by estrogen deficiency in lipid metabolism. This study encompassed direct measurements of plasma biochemical analyses, liver lipid contents, and assessments of the mitochondrial β-oxidation capacity as well as an evaluation of the liver redox status in an animal model of estrogen deficiency. When compared with control mice, the livers of ovariectomized (OVX) mice presented considerable accretions in their lipid contents, which were accompanied by increased levels of lipid peroxidation in liver homogenates and mitochondria from OVX groups and decreased reduced glutathione (GSH) contents. In isolated mitochondria, estrogen deficiency inhibited mitochondrial β-oxidation of fatty acids irrespective of their chain length. The liver mitochondrial and peroxisomal H2O2 generations in OVX mice were increased. Additionally, the activities of all antioxidant enzymes assessed were decreased. These data provide one potential explanation for the increased susceptibility to metabolic diseases observed after menopause.

Variation of lipids and fatty acids composition in the tissues of wild devil stinger (Inimicus japonicas) during sexual maturation

The present study was conducted to characterize the lipid and fatty acid profiles in different tissues (gonad, liver and muscle) of the wild-caught devil stinger during sexual maturation. Wild-caught devil stinger were divided into six groups according to gonad development and gender. Total lipid content was up to 40% dry weight in liver and was significantly higher than in other tissues (ovary, testis and muscle) in both male and female stinger during sexual maturation. During maturation, total lipid content in the female stinger liver decreased, but in males significantly increased in all tissues. Higher proportions of neutral lipids (NL) were observed in the stinger liver, while polar lipids (PL) were mainly quantified in the gonad and muscle of both male and female stinger. The PL content of the ovary significantly decreased with sexual maturation, but NL were significantly increased. The fatty acids composition of the stinger broodstocks were tissue- and lipid class-specific. In the stinger gonad high-unsaturated fatty acids (HUFA), such as ARA, DHA and EPA, are selectively transferred and conserved, indicating the crucial role of these fatty acids during sexual maturation of this fish species.

Saturated lipids are more effective than others in juvenile California yellowtail feeds—Understanding and harnessing LC-PUFA sparing for fish oil replacement

Diet-to-tissue transfer of long-chain polyunsaturated fatty acids (LC-PUFAs) is more efficient when diets contain saturated fatty acid (SFA) or monounsaturated fatty acid (MUFA)-rich alternative lipids. This mechanism, the omega-3 or LC-PUFA “sparing effect”, encourages more efficient metabolism of the limited LC-PUFAs available in terms of their important physiological functions and tissue retention, and the likelihood of successful fish oil sparing (i.e. complete fish oil replacement maintaining growth and tissue fatty acid profile). However, it is still unclear whether dietary SFAs and MUFAs are equivalent or interact synergistically or antagonistically in this context. Accordingly, we compared production performance and tissue fatty acid composition of California Yellowtail fed diets containing fish oil (rich in LC-PUFAs) or soybean oil (rich in C18 PUFAs), partially hydrogenated soybean oil (rich in MUFAs), fully hydrogenated soybean oil (rich in SFAs), or blends of these soybean oils. After 10 weeks, production performance was not affected by dietary lipid source or fatty acid composition, and tissue fatty acid profiles generally mimicked dietary fatty acid composition. However, tissues of fish fed SFA-rich lipids exhibited the greatest similarity to those fed fish oil, and fillets of fish fed fully hydrogenated soybean oil had significantly higher levels of LC-PUFAs (43.9 g LC-PUFA /100 g fatty acid methyl esters; FAMEs) than those fed any of the other diets (22.5–36.9 g LC-PUFA /100 g FAMEs), including the LC-PUFA-rich fish oil-based feed (39.8 g LC-PUFA /100 g FAMEs). Power regression analyses demonstrated a stronger positive relationship between dietary SFAs with fillet LC-PUFA deposition (r2 = 0.73) than dietary MUFAs (r2 = 0.09), whereas dietary C18 PUFAs were observed to have a negative relationship with fillet LC-PUFA content (r2 = 0.85). These trends were also observed in liver and eye tissues, and to a lesser extent in brain tissue. Multiple linear regression analyses demonstrated a stronger relationship between dietary levels of PUFAs and SFAs and tissue fatty acid profile composition, including LC-PUFA content, than dietary levels of PUFAs and MUFAs. Fillet lipid content varied significantly, with the FISH and C18 PUFA SOY diets displaying the highest levels. The same pattern was observed for liver lipid content, but not significantly. Our findings suggest that SFAs are the primary drivers of LC-PUFA sparing, whereas MUFAs exert a weaker independent sparing effect and appear to diminish the sparing effect of dietary SFAs when MUFAs were also present.

Micheliolide alleviates hepatic steatosis in db/db mice by inhibiting inflammation and promoting autophagy via PPAR-γ-mediated NF-кB and AMPK/mTOR signaling

The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated from Michelia champaca were previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment. Similarly, MCL also attenuated the inflammatory responses and lipid accumulation in LM-treated AML12 and L02 cells by upregulating PPAR-γ and decreasing p-IкBα and p-NF-κB/p65, thereby inhibiting the NF-κB pathway and reducing lipotoxicity. Furthermore, MCL administration increased LC3B, Atg7 and Beclin-1 expression and the LC3B-II/I ratio in db/db mouse livers and LM-treated AML12 and L02 cells, and these MCL-induced increases were mediated by the activation of PPAR-γ and p-AMPK and inhibition of p-mTOR and induce autophagy. These effects were blocked by PPAR-γ and AMPK inhibitors. Our findings suggest that MCL ameliorates liver steatosis by upregulating PPAR-γ expression, thereby inhibiting NF-κB-mediated inflammation and activating AMPK/mTOR-dependent autophagy.

Effect of high chronic intake of sucrose on liver metabolism in aging rats. Modulation by rutin and micronutrients.

High-sugar intake and senescence share common deleterious effects, in particular in liver, but combination of these two factors was little studied. Our aims were to examine the effect of a high-sucrose diet in liver of old rats and also the potential benefices of a polyphenol/micronutrient supplementation. Four groups of 22-month-old male rats fed during 5months with a diet containing either 13 or 62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc were compared. We measured liver macronutrient composition, glycation/oxidative stress, enzyme activities (lipogenesis, β-oxidation, fructokinase), gene expression (enzymes and transcription factors), in vivo protein synthesis rates and plasma parameters. Sucrose induced an increase in plasma and liver lipid content, and a stimulation of liver protein synthesis rates. Gene expression was little changed by sucrose, with lower levels for LXR-α and LXR-β. Polyphenol/micronutrient supplementation tended to limit liver triglyceride infiltration through variations in fatty acid synthase, acyl coA oxidase, and possibly ATP-citrate lyase activities. In conclusion, despite differences in enzymatic regulations, and blunted responses of gene expression, high-sucrose diet was still able to induce a marked increase in liver lipid content in old animals. However, it probably attenuated the positive impact of polyphenol/micronutrients.

High level of dietary soybean oil depresses the growth and anti-oxidative capacity and induces inflammatory response in large yellow croaker Larimichthys crocea

Increasing demand, uncertain availability and high price of fish oil with the expansion of aquaculture made it essential to search alternative lipid sources. Vegetable oil has been proved to be the best candidate for the replacement of fish oil in aquafeeds. However, this replacement especially in high level potentially has some negative effects on fish. The present study was conducted to investigate the growth performance, anti-oxidative and inflammatory responses of large yellow croaker to replacement of dietary fish oil by soybean oil. Three isonitrogenous (46% crude protein) and isolipidic (13% crude lipids) diets were formulated to feed fish (initial body weight: 36.80 ± 0.39 g) for 12 weeks. The control diet was designed to contain 6.5% of fish oil, and named as FO. On the basis of the control diet, the fish oil was 50% and 100% replaced by soybean oil, and these two diets were named as FS and SO, respectively. Results showed that the specific growth rate significantly decreased in the SO group. Crude lipid contents in muscle and liver of fish fed SO diet were significantly higher than those in the FO group. The ratio of n-3 poly-unsaturated fatty acids (PUFAs) to identified fatty acids in liver decreased significantly, while n-6 PUFAs increased significantly with increasing dietary soybean oil inclusion. The levels of triacylglycerol, non-esterified fatty acid and tumour necrosis factor α, and the activity of aspartate aminotransferase in serum significantly increased in SO group. The total anti-oxidative capacity and expressions of the anti-oxidation-related genes (superoxide dismutase 1 and 2, catalase, glutathion peroxidase and nuclear factor erythroid 2-related factor 2) were significantly decreased by dietary soybean inclusion. Dietary soybean oil significantly decreased the gene expressions of the anti-inflammatory cytokines (arginase I and interleukin 10), and increased the pro-inflammatory cytokines (tumour necrosis factor α and interleukin 1β). The replacement of dietary fish oil by soybean oil also induced an over-expression of toll-like receptor 22 and myeloid differentiation factor 88 in liver. In conclusion, dietary soybean oil could suppress growth performance and liver anti-oxidative capacity, and induce inflammatory responses of large yellow croaker.

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation.

Maternal obesity (MO) and exposure to a high-fat, high-simple-carbohydrate diet during pregnancy predisposes offspring to obesity, metabolic and cardiovascular disorders in later life. Underlying molecular pathways and potential epigenetic factors that are dysregulated in MO were identified using unbiased transcriptomic methods. There was increased lipid accumulation and severe steatosis in the MO baboon fetal liver suggesting that these offspring are on an early trajectory of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high-fat, high-fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β-catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non-human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption.

Insulinotropic Effect of S-Allyl Cysteine in Rat Pups.

S-Allyl cysteine (SAC) is found in garlic and has been reported to exert antidiabetic and antiobesity properties in drug-induced adult experimental models of metabolic dysfunction, but its potential beneficial effects in high-fructose diet neonatal rat models have not been determined. This study investigated the potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and female (n=32) Wistar rat pups, were randomly assigned to and administered the following treatment regimens daily for 15 days: group I, distilled water; group II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS. The pups’ blood glucose, triglyceride, cholesterol, plasma leptin and insulin concentration, liver lipid content, and liver histology were determined at termination. In female rat pups, orally administered SAC prevented FS-induced hypoinsulinemia but significantly increased (P≤0.05) liver lipid content. Oral administration of SAC significantly increased (P≤0.05) plasma insulin concentration and homeostasis model assessment for insulin resistance in the male pups. The potential sexually dimorphic effects of SAC (insulinotropic effects in male pups and protection of female pups against fructose-induced hypoinsulinemia) suggest that SAC could be potentially exploited as an antidiabetic and insulinotropic agent. Caution should, however, be exercised in the use of SAC during suckling as it could result in excessive liver lipid accumulation and insulin resistance.

Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation.

Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3days after the stroke. Protein-energy status was assessed by a combination of body weight, food intake, serum acute phase proteins and corticosterone, and liver lipid content. Deficits in motor function were evaluated in the horizontal ladder walking and cylinder tasks at 3days after stroke. The glial response and brain elemental signature were investigated by immunohistochemistry and micro-X-ray fluorescence imaging, respectively. The LP-fed rats reduced food intake, resulting in PEM. Pre-existing PEM augmented stroke-induced abnormalities in forelimb placement accuracy on the ladder; LP-St rats made more errors (29 ± 8%) than the NP-St rats (15 ± 3%; P < 0.05). This was accompanied by attenuated astrogliosis in the peri-infarct area by 18% and reduced microglia activation by up to 41 and 21% in the peri-infarct area and the infarct rim, respectively (P < 0.05). The LP diet altered the cortical Zn, Ca, and Cl signatures (P < 0.05). Our data suggest that proactive treatment of pre-existing PEM could be essential for optimal post-stroke recovery.

Effect of an artificial Ascaridia galli infection on egg production, immune response, and liver lipid reserve of free-range laying hens

This study was conducted to determine the effect of Ascaridia galli infection on free-range laying hens. Lohmann Brown laying hens (n = 200) at 17 wk of age were allocated to 4 treatment groups (n = 50 per group), each with 5 replicate pens of 10 hens. Hens in 3 treatment groups were orally inoculated with different doses of embryonated A. galli eggs: low (250 eggs), medium (1,000 eggs), and high (2,500 eggs) levels, whereas hens of the control group were not infected. Infection levels were monitored using excreta egg counts and mature A. galli worm counts in the intestine. Anti A. galli antibody titers (IgY) in the serum were measured prior to infection, and at 6, 11, 15, and 20 wk post infection (PI) and in egg yolk at 11 and 20 wk PI. Parameters evaluated included feed intake, egg production, egg weight, egg mass, FCR, liver weight, liver fat, and intra epithelial immune cell infiltration. The results showed no difference in feed intake, body weight, or FCR among any treatment groups (P > 0.05). Egg production was lower in the low infection group compared to other groups at 20 wk of age (P < 0.01). Serum IgY was higher in the infected groups’ hens at 20 wk PI compared to control group hens (P < 0.01). Yolk IgY increased significantly over time and was higher in infected hens compared to hens of the control group at 11 and 20 wk PI (P < 0.001). No differences were observed in liver lipid content or intraepithelial lymphocytes infiltration among treatment groups. Ascaridia galli eggs in the coprodeum content and adult A. galli worm count were higher in infected hens compared to hens of the control group (P < 0.01). In conclusion, the effects of artificial infection with A. galli on the parameters investigated were minor, and egg yolk antibody may be a more reliable indicator of A. galli infection than serum antibody or excreta egg count.

Influence of age, size and condition factor on lipid concentration in the snapper Chrysophrys auratus

ABSTRACTSurvival, growth rates and functionality of larvae have been hypothesised to correlate with higher lipid provisioning in older teleosts. To test the lipid provisioning part of this hypothesis, we investigated the total and relative (mg/g) lipid (triglyceride) concentration in both the source (liver) and sink (gonad) lipidation organs of female snapper Chrysophrys auratus across age, size and condition factor throughout its spawning season. Age, size and condition factor had little discernible effect on the total or relative lipid concentration in either liver or gonadal tissue. Therefore, if oocyte quality (based on triglyceride concentration) is comparable across a population, research on the relationship between lipidomics and reproductive success needs to move beyond highlighting correlations to elucidating causation by focusing on the biochemical mechanisms of egg quality and larval survival, identifying maternal parameters associated with consistent lipid provisioning, and partitioning of phenotypic and genotypic maternal influences.

Anti-hypercholesterolemic Effect of Berbamine Isolated from Rhizoma Coptidis in Hypercholesterolemic Zebrafish Induced by High-Cholesterol Diet.

The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery was reduced dose-dependently after BBM treatment. For adult zebrafish, administration of 0.2% BBM exhibited a significant decrease in plasma total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) levels by 37%, 38% and 28%, respectively, along with a fall in lipid content in liver. Further investigation suggested that the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and microsomal triglyceride transfer protein (MTP) in liver were down-regulated and the transcription levels of liver gene low-density lipoprotein receptor (LDLR) and cytochrome P450 polypeptide 1a of subfamily A of family 7 (CYP7A1a) were significantly up-regulated with BBM treatment. Histological study showed that BBM can alleviate hepatic steatosis induced by HC diet. These data suggested that BBM has anti-hypercholesterolemic and hepatoprotective effects. The mechanism probably related to the up-regulation of cholesterol transport and bile acid synthesis as well as inhibition of cholesterol synthesis and lipoprotein assembly or secretion.

Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content.

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements.Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²).Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.

Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

Background/Aims: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration. Methods: 2/3 partial hepatectomy (PH) was performed in wild type C57BL/6J (WT) and Srebp-1c-/- mice. The lipid contents in serum and liver were measured by enzymatic colorimetric methods. Hepatic lipid droplets were detected by Oil Red O staining and immunohistological staining. Hepatic expression of genes involved in lipid metabolism and cellular proliferation was determined by real-time PCR and/or immunoblot. Hepatocyte proliferation and liver regeneration were assessed by BrdU staining and the weight of remanent liver lobes in Srebp-1c-/- mice, respectively. Results: Srebp-1c-/- mice displayed reduced triglyceride and fatty acids but increased cholesterol in the liver before PH. In response to PH, hepatocellular DNA synthesis was elevated and cell cycle progression was prolonged in Srebp-1c-/- mice, which was associated with enhanced liver regeneration. However, Srebp-1c-/- mice had comparable triglyceride and fatty acid contents and expressions of related genes compared with WT mice during the liver regeneration. In contrast, SREBP-1c-deficiency-induced alteration of cholesterol metabolism was retained during the liver regeneration after PH. Srebp-1c-/- mice exhibited higher cholesterol contents and enhanced expression of SREBP-2 and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in the liver than WT mice after PH. Moreover, downregulation of genes involved in cholesterol elimination was observed after PH in Srebp-1c-/- mice. Conclusion: SREBP-1c deficiency in mice did not interfere with triglyceride and fatty acid metabolism but was associated with significant changes in cholesterol profiles during liver regeneration after PH. These results suggest that increased hepatocellular cholesterol storage and cholesterol availability with the enhanced liver regeneration are identified in Srebp-1c-/- mice. This study also shows that providing requisite cholesterol levels to proliferating hepatocytes and keeping appropriate cholesterol metabolism are required for normal liver regeneration.