Effect of Intracerebroventricular Administration of Galanin-Like Peptide on Hepatokines in C57BL/6 J Mice.

Galanin-like peptide (GALP) is a neuropeptide that was first isolated and identified from the porcine hypothalamus. Studies have described an anti-obesity effect of GALP. We previously found that intracerebroventricular administration of GALP in mice resulted in an increase in respiratory exchange rate 12 to 16 h later. GALP may also affect glucose metabolism, but the detailed mechanism has not been elucidated. In this study, we investigated the effects of GALP on glucose and lipid metabolism in the liver. Nine-week-old male C57BL / 6 J mice were administered a single intracerebroventricular dose of saline or GALP and dissected 16 h later. There were no significant between-group differences in body weight and blood glucose levels. With regard to gene and protein expression, G6Pase associated with hepatic gluconeogenesis was significantly reduced in the GALP group. In addition, the hepatokines selenoprotein P and fetuin-A, which induce insulin resistance in the liver, were significantly decreased in the GALP group. These results suggest that intracerebroventricular administration of GALP decreases the expression of key hepatokines, thereby enhancing glucose metabolism.

Fish oil consumption prevents hepatic lipid accumulation induced by high-cholesterol feeding in obese KK mice.

Fish oil (FO) is rich in the n-3 polyunsaturated fatty acids. It has been demonstrated that FO intake possesses lipid-lowering properties. Conversely, a high-cholesterol (CH) diet promotes lipid accumulation in the liver and induces fatty liver. This study investigated the effects of FO feeding on hepatic lipid accumulation induced by high-cholesterol feeding in KK mice. All experimental diets had a fat energy ratio of 25%, the SO group had all fat sources as safflower oil (SO), the 12.5 FO group had half of the SO replaced with FO, and the 25 FO group had all of the SO replaced with FO, each with or without 2 weight % (wt%) cholesterol (SO/CH, 12.5 FO/CH, and 25 FO/CH groups, respectively), for 8 weeks. The hepatic triglyceride and total cholesterol levels were significantly lower in the 25 FO/CH group than in the SO/CH group. The hepatic mRNAs of fatty acid synthesis-related genes were downregulated by the FO feeding groups. In view of importance to establish the benefit of FO for preventing severe NAFLD, our results suggest that FO intake prevents excessive hepatic fat accumulation induced by a high-cholesterol diet in obese KK mice through the inhibition of fatty acid synthesis.

Fish oil-derived n-3 polyunsaturated fatty acids downregulate aquaporin 9 protein expression of liver and white adipose tissues in diabetic KK mice and 3T3-L1 adipocytes.

Aquaporin 9 (AQP9) is an integral membrane protein that facilitates glycerol transport in hepatocytes and adipocytes. Glycerol is necessary as a substrate for gluconeogenesis in the physiological fasted state, suggesting that inhibiting AQP9 function may be beneficial for treating type 2 diabetes associated with fasting hyperglycemia. The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are rich in fish oil and lower the risk of metabolic syndrome; however, the effects of EPA and DHA on AQP9 expression in obese and type 2 diabetes are unclear. The KK mouse is an animal model of obesity and type 2 diabetes because of the polymorphisms on leptin receptor gene, which results in a part of cause for obese and diabetic conditions. In this study, we determined the effect of fish oil-derived n-3 PUFA on AQP9 protein expression in the liver and white adipose tissue (WAT) of KK mice and mouse 3T3-L1 adipocytes. The expression of AQP9 protein in the liver, epididymal WAT, and inguinal WAT were markedly decreased following fish oil administration. We also demonstrated that n-3 PUFAs, such as DHA, and to a lesser extent EPA, downregulated AQP9 protein expression in 3T3-L1 adipocytes. Our results suggest that fish oil-derived n-3 PUFAs may regulate the protein expressions of AQP9 in glycerol metabolism-related organs in KK mice and 3T3-L1 adipocytes.

Association of Aquaporin 7 and 9 with Obesity and Fatty Liver in db/db Mice.

Aquaporin (AQP) 7 and AQP9 are membrane channel proteins called aquaglyceroporins and are related to glucose and lipid metabolism. AQP7 is mainly expressed in white adipose tissue (WAT) and is involved in releasing glycerol into the bloodstream. AQP9 is the glycerol channel in the liver that supplies glycerol to the hepatic cells. In this study, we investigated the relationship between the expression of aquaglyceroporins and lifestyle-related diseases, such as obesity and fatty liver, using 22-week-old db/db mice. Body weight, WAT, and liver weight showed increases in db/db mice. The levels of liver lipids, plasma lipids, insulin, and leptin were also increased in db/db mice. Gene expression related to fatty acid and triglyceride synthesis in the liver was enhanced in db/db mice. In addition, gene and protein expression of gluconeogenesis-related enzymes was increased. Conversely, lipolysis-related gene expression in WAT was reduced. In the db/db mice, AQP9 expression in the liver was raised; however, AQP7 expression in WAT was reduced. These results suggest that in db/db mice, enhanced hepatic AQP9 expression increased the supply of glycerol to the liver and induced fatty liver and hyperglycemia. Additionally, reduced AQP7 expression in WAT is associated with excessive lipid accumulation in adipocytes. Aquaglyceroporins are essential molecules for glucose and lipid metabolism, and may be potential target molecules for the treatment of obesity and lifestyle-related diseases.

Phenotypic and genotypic changes in obesity and type 2 diabetes of male KK mice with aging.

Research into the prevention and treatment of age-related metabolic diseases are important in the present-day situation of the aging population. We propose that an elderly diabetic mouse model may be useful to such research as it exhibits deterioration of glucose and lipid metabolism. Although the KK mouse strain is commonly used as a model of moderate obesity and type 2 diabetes, the utility of this strain as an elderly obese and diabetic model mouse for research into aging remains unclear. The present study aimed to investigate age-related changes of glucose and lipid metabolism in male KK mice fed a standard chow diet. We demonstrate that 40 weeks KK mice exhibit age-related dysfunctions, such as development of insulin resistance associated with pancreatic islet hypertrophy and decreased lipolysis in white adipose tissue (WAT) compared with 15 weeks KK mice. However, aging does not appear to cause mitochondrial dysfunction of brown adipose tissue. Unexpectedly, hyperglycemia, potential glucose uptake in insulin-sensitive organs, hepatic lipid accumulation, hypertrophy of adipocytes, and inflammation in epididymal WAT did not worsen but rather compensated in 40 weeks KK mice. Our data indicate that the use of male KK mice as an elderly obese and diabetic mouse model has some limitations and in order to represent a useful elderly obese and diabetic animal model, it may be necessary to induce deterioration of glucose and lipid metabolism in KK mice through breeding with high-sucrose or high-fat diets.

Differential Gene Expression in Longissimus Dorsi Muscle of Hanwoo Steers-New Insight in Genes Involved in Marbling Development at Younger Ages.

The Korean Hanwoo breed possesses a high capacity to accumulate intramuscular fat, which is measured as a marbling score in the beef industry. Unfortunately, the development of marbling is not completely understood and the identification of differentially expressed genes at an early age is required to better understand this trait. In this study, we took muscle samples from 12 Hanwoo steers at the age of 18 and 30 months. From the contrast between age and marbling score, we identified in total 1883 differentially expressed genes (FDR < 0.05 and logarithm fold change ≥ 1.5) with 782 genes up-regulated and 1101 down-regulated. Differences in gene expression were higher between the ages x marbling groups rather than between high and low marbling groups. At 18 months of age, the genes SLC38A4, ABCA10, APOL6, and two novel genes (ENSBTAG00000015330 and ENSBTAG00000046041) were up-regulated in the high marbling group. From the protein-protein interaction network analysis, we identified unique networks when comparing marbling scores between different ages. Nineteen genes (AGT, SERPINE1, ADORA1, FOS, LEP, FOXO1, FOXO3, ADIPOQ, ITGA1, SDC1, SDC4, ITGB3, ITGB4, CXCL10, ACTG2, MX1, EDN1, ACTA2, and ESPL1) were identified to have an important role in marbling development. Further analyses are needed to better understand the role of these genes.

Impact of discontinuation of fish oil after pioglitazone-fish oil combination therapy in diabetic KK mice.

Pioglitazone is one of the thiazolidinediones (TZDs) and an insulin-sensitive drug for type 2 diabetes. In our previous study, a combination of pioglitazone and fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) was shown to inhibit pioglitazone-induced side effects, such as accumulation of subcutaneous fat and body weight gain. However, the effects of the discontinuation of fish oil after combination treatment with TZD and fish oil are not clear. In this study, discontinuation of fish oil for 4 weeks showed several unfavorable effects: (1) return of plasma adiponectin level, (2) reversal of the inhibition of lipogenesis and activation of fatty acid ß-oxidation in liver, (3) increase in hypertrophic adipocytes in epidydimal white adipose tissue (WAT) and (4) accumulation of lipids in brown adipose tissue (BAT). However, insulin resistance was ameliorated by pioglitazone with or without fish oil treatment and the discontinuation of fish oil. These findings indicate that discontinuation of n-3 PUFA after combination therapy with TZDs adversely affects lipid metabolism and energy homeostasis in liver, epididymal WAT and BAT.

Molecular regulation of skeletal muscle mass and the contribution of nitric oxide: A review.

A variety of internal and external factors such as exercise, nutrition, inflammation, and cancer-associated cachexia affect the regulation of skeletal muscle mass. Because skeletal muscle functions as a crucial regulator of whole body metabolism, rather than just as a motor for locomotion, the enhancement and maintenance of muscle mass and function are required to maintain health and reduce the morbidity and mortality associated with diseases involving muscle wasting. Recent studies in this field have made tremendous progress; therefore, identification of the mechanisms that regulate skeletal muscle mass is necessary for the physical and nutritional management of both athletes and patients with muscle wasting disease. In this review, we present an overall picture of the interactions regulating skeletal muscle mass, particularly focusing on the insulin-like growth factor-I (IGF-I)/insulin-Akt-mammalian target of rapamycin (mTOR) pathway, skeletal muscle inactivity, and endurance and resistance exercise. We also discuss the contribution of nitric oxide (NO) to the regulation of skeletal muscle mass based on the current knowledge of the novel role of NO in these processes.

Benefits of combination low-dose pioglitazone plus fish oil on aged type 2 diabetes mice.

The elderly patients with type 2 diabetes suffer more adverse drug events than young adults due to pharmacokinetic and pharmacodynamic changes associated with aging. Reducing the risks of these medication-related problems are equally important for the clinical care of older type 2 diabetes patients. Pioglitazone is used for treating type 2 diabetes as an oral antidiabetic drug. Despite pioglitazone is used helpful insulin sensitizers, the accumulation of subcutaneous fat is considered a major adverse effect of pioglitazone therapy. We investigated to reduce the adverse effect of pioglitazone by combination with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in aged diabetic KK mice. The accumulation of subcutaneous fat associated with high-dose pioglitazone is reduced by fish oil, suppressing lipogenesis and stimulating fatty acid ß-oxidation in the liver. Our data suggest that adding fish oil to low-dose pioglitazone results in antidiabetic efficacy similar to that of the high-dose without concomitant body weight gain.

Fish oil and fenofibrate inhibit pancreatic islet hypertrophy, and improve glucose and lipid metabolic dysfuntions with different ways in diabetic KK mice.

We examined the effects of fish oil and fenofibrate (FF) on the pancreatic islet hypertrophy, and on the modification of glucose and lipid metabolic dysfunctions in KK mice with insulin resistance. The mice were fed one of four diets [25en% lard/safflower oil (LSO), 25en% fish oil (FO), or each of these diets plus 0.1wt% FF (LSO/FF, FO/FF)] for 9 weeks. FO group and both FF groups had significantly lower final body and adipose tissue weights than LSO group. Pancreatic islet hypertrophy was observed only in LSO group but not in the other groups with fish oil or FF. And, it is likely that fish oil has a stronger therapeutic effect on islet hypertrophy. Plasma adiponectin level was significantly higher in FO group but not in both FF groups. Expression of hepatic lipogenic enzyme genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) was lower in FO groups with or without FF, whereas fatty acid oxidation-related mRNAs such as acyl-CoA oxidase (AOX) and uncoupling protein-2 (UCP-2) were more abundant in FF groups with or without fish oil. Our results suggest that both fish oil and FF improve pancreatic islet hypertrophy with the amelioration of insulin resistance. Fish oil enhances insulin sensitivity by increasing plasma adiponectin; however, the beneficial effect of FF on insulin resistance seems to be independent of the plasma adiponectin level. These results mean that improvement of glucose and lipid metabolic dysfuctions in diabetic KK mice are independently approached by fish oil and FF.

Effect of Intranasal Administration of Galanin-like Peptide (GALP) on Body Weight and Hepatic Lipids Accumulation in Mice with Diet-induced Obesity.

Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of food intake behavior, body weight and energy metabolism. In previous studies, we demonstrated that the intranasal administration of GALP has weight loss effects, although the mechanism of this action was not clarified. The aim of this study was to demonstrate the functional significance of GALP on lipid metabolism in the liver. Mice were fed a high fat diet to cause diet-induced obesity (DIO) and then administered GALP intranasally for 2 weeks (experimental), or vehicle (control). Body weights, along with lipid levels in the plasma and liver, and lipid metabolism-related gene expression in the liver were subsequently measured. Body weight gain was decreased by the GALP treatment compared to the control group. Lipid droplet levels in hepatocytes and hepatic triglyceride levels were decreased in the GALP group compared with the vehicle group, whereas hepatic fatty acid ß-oxidation-related gene mRNA levels were increased in the GALP group. These results suggest that the intranasal administration of GALP has an inhibitory effect on lipid accumulation in the liver.

Protective effects of fish oil and pioglitazone on pancreatic tissue in obese KK mice with type 2 diabetes.

n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic ß-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas. To answer this question, KK mice, which serve as a model for obesity and type 2 diabetes, were treated for 8 weeks with fish oil and pioglitazone. The combined regimen suppressed pancreatic islet hypertrophy (mean islet area decreased by an average of 49% vs. control) compared with mice treated with fish oil or pioglitazone alone (decreased by an average of 21% and 32% vs. control, respectively). Compared with the controls, individual or combined treatment significantly increased the percentage of ß-cell area in the pancreatic islets, significantly decreased endoplasmic reticulum stress, and reduced the percentage of apoptotic cell death in the pancreatic islets. These findings suggest that fish oil and/or pioglitazone prevents ß-cell dysfunction by improving the insulin resistance and decreasing the ER stress.

Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8.

This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+ WME) supplemented diet for 26 weeks were subjected to four behavioral tests - open field, Y-maze, new object recognition, and water-filled multiple T-maze - to examine effects on learning and memory. Brain transcriptome of SAMP8 mice-fed the WME diet over control low-safflower oil (LSO) diet-fed mice was delineated on a 4 × 44 K mouse whole genome DNA microarray chip. Results revealed the WME diet not only induced improvements in the learning and memory formation but also positively modulated changes in the brain of the SAMP8 mouse; the gene inventories are publically available for analysis by the scientific community. Interestingly, the SAMP8 mouse model presented many genetic characteristics of AD, and numerous novel molecules (Slc2a5, Treh, Fbp1, Aldob, Ppp1r1a, DNase1, Agxt2l1, Cyp2e1, Acsm1, Acsm2, and Pah) were revealed over the SAMR1 (senescence-accelerated mouse resistant 1) mouse, to be oppositely regulated/recovered under the balenine (+ WME) supplemented diet regime by DNA microarray and bioinformatics analyses. Our present study demonstrates an experimental strategy to understand the effects of dipeptide balenine, prominetly contained in meat diet, on SAMP8, providing new insight into whole brain transcriptome changes genome-wide. The gene expression data has been deposited into the Gene Expression Omnibus (GEO): GSE76459. The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation.

Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue.

Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals, and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP-treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid ß-oxidation in liver and lipolysis in adipose tissue, and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system.

The relationship between aquaglyceroporin expression and development of fatty liver in diet-induced obesity and ob/ob mice.

Aquaporin (AQP) 7 and AQP9 are subcategorised as aquaglyceroporins which transport glycerin in addition to water. These AQPs may play a role in the homeostasis of energy metabolism. We examined the effect of AQP7, AQP9, and lipid metabolism-related gene expression in obese mice. In diet-induced obese (DIO) mice, excess lipid accumulated in the liver, which was hyperleptinemic and hyperinsulinemic. Hepatic AQP9 gene expression was significantly increased in both DIO and ob/ob mice compared to controls. The mRNA expression levels of fatty acid and triglyceride synthesis-related genes and fatty acid ß oxidation-related genes in the liver were also higher in both mouse models, suggesting that triglyceride synthesis in this organ is promoted as a result of glycerol release from adipocytes. Adipose AQP7 and AQP9 gene expressions were increased in DIO mice, but there was no difference in ob/ob mice compared to wild-type mice. In summary, adipose AQP7 and AQP9 gene expressions are increased by diet-induced obesity, indicating that this is one of the mechanisms by which lipid accumulates in response to a high fat diet, not the genetic mutation of ob/ob mice. Hepatic AQP9 gene expression was increased in both obesity model mice. AQP7 and AQP9 therefore have the potential of defining molecules for the characterisation of obesity or fatty liver and may be a target molecules for the treatment of those disease.

Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice.

Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis.

Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.

Hesperidin prevents androgen deficiency-induced bone loss in male mice.

The purpose of this study was to examine whether hesperidin inhibits bone loss in androgen-deficient male mice. Male ddY mice aged 7 weeks underwent either a sham operation or orchidectomy (ORX) and were divided into five groups: a sham-operated group fed a control diet (Sham) based on AIN-93G formulation with corn oil instead of soy bean oil, an ORX group fed the control diet (ORX), a group fed the control diet containing 0.5% hesperidin (ORX + H), a group fed the control diet containing 0.7% α-glucosylhesperidin (ORX + αG), and a group fed the control diet containing 0.013% simvastatin (ORX + St). Four weeks after intervention, ORX mice showed a striking decrease in seminal vesicle weight, which was not affected by the administration of hesperidin, α-glucosylhesperidin, or simvastatin. Femoral BMD was significantly reduced by ORX, and bone loss was inhibited by the administration of hesperidin, α-glucosylhesperidin or simvastatin. Histomorphometric analysis showed that the bone volume and trabecular thickness were significantly lower, and the osteoclast number was higher in the distal femoral cancellous bone in the ORX group than in the Sham group, and these were normalized in the ORX + H, ORX + αG and ORX + St groups. These results indicate that hesperidin inhibited bone resorption and hyperlipidemia, in ORX mice, and the preventive effect was stronger than that observed in ovariectomized mice in our previous study.

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.

Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice.

We examined the effects of low-dose fish oil ingestion on hepatic lipid accumulation caused after high cholesterol feeding in C57BL/6J mice. The mice were fed purified experimental diets consisting of 20 energy % (en%) safflower oil (SO or SO/CH), 2 en% fish oil + 18 en% safflower oil (2FO or 2FO/CH), or 5 en% fish oil + 15 en% safflower oil (5FO or 5FO/CH) with or without 2 weight % (wt %) cholesterol for 8 weeks. Hepatic triglyceride and total cholesterol contents were significantly lower in groups that were fed diets containing fish oil and cholesterol than in those that were fed safflower oil and cholesterol. The hepatic mRNA levels of fatty acid synthase (FAS) were lower in groups fed cholesterol or fish oil. Fatty acid oxidation-related hepatic gene expressions were higher in fish oil-fed groups. Fecal cholesterol excretion was higher in all cholesterol-fed groups; cholesterol excretion was high in groups fed fish oil and cholesterol. These results suggest that low-dose fish oil diets improve lipid metabolism by modifying the expression of lipid metabolism-related genes in the liver and increasing fecal cholesterol excretion.