Differential Effects of Krill Oil and Fish Oil on the Hepatic Transcriptome in Mice

Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil (FO) or krill oil (KO). We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (KO) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that KO-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from FO modulated fewer pathways than a KO-supplemented diet and did not modulate key metabolic pathways regulated by KO, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, FO upregulated the cholesterol synthesis pathway, which was the opposite effect of krill-supplementation. Neither diet elicited changes in plasma levels of lipids, glucose, or insulin, probably because the mice used in this study were young and were fed a low-fat diet. Further studies of KO-supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects

The Role of PPARα Activation in Liver and Muscle

PPARα is one of three members of the soluble nuclear receptor family called peroxisome proliferator-activated receptor (PPAR). It is a sensor for changes in levels of fatty acids and their derivatives that responds to ligand binding with PPAR target gene transcription, inasmuch as it can influence physiological homeostasis, including lipid and carbohydrate metabolism in various tissues. In this paper we summarize the involvement of PPARα in the metabolically active tissues liver and skeletal muscle and provide an overview of the risks and benefits of ligand activation of PPARα, with particular consideration to interspecies differences

Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic Agents

Adipose tissue metabolism is closely linked to insulin resistance, and differential fat distributions are associated with disorders like hypertension, diabetes, and cardiovascular disease. Adipose tissues vary in their impact on metabolic risk due to diverse gene expression profiles, leading to differences in lipolysis and in the production and release of adipokines and cytokines, thereby affecting the function of other tissues. In this paper, the roles of the various adipose tissues in obesity are summarized, with particular focus on mitochondrial function. In addition, we discuss how a functionally mitochondrial-targeted compound, the modified fatty acid tetradecylthioacetic acid (TTA), can influence mitochondrial function and decrease the size of specific fat depots

Tissue-Specific Effects of Bariatric Surgery Including Mitochondrial Function

A better understanding of the molecular links between obesity and disease is potentially of great benefit for society. In this paper we discuss proposed mechanisms whereby bariatric surgery improves metabolic health, including acute effects on glucose metabolism and long-term effects on metabolic tissues (adipose tissue, skeletal muscle, and liver) and mitochondrial function. More short-term randomized controlled trials should be performed that include simultaneous measurement of metabolic parameters in different tissues, such as tissue gene expression, protein profile, and lipid content. By directly comparing different surgical procedures using a wider array of metabolic parameters, one may further unravel the mechanisms of aberrant metabolic regulation in obesity and related disorders

Krill oil attenuates left ventricular dilatation after myocardial infarction in rats

Background: In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. Results: The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. Conclusions: Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling

Serum trans fatty acids, asymmetric dimethylarginine and risk of acute myocardial infarction and mortality in patients with suspected coronary heart disease: a prospective cohort study

Quartiles of trans 16:1n7 and risk of acute myocardial infarction, cardiovascular death and all-cause mortality. (DOCX 20 kb

Disturbed lipid profile in common variable immunodeficiency – a pathogenic loop of inflammation and metabolic disturbances

The relationship between metabolic and inflammatory pathways play a pathogenic role in various cardiometabolic disorders and is potentially also involved in the pathogenesis of other disorders such as cancer, autoimmunity and infectious diseases. Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults, characterized by increased frequency of airway infections with capsulated bacteria. In addition, a large proportion of CVID patients have autoimmune and inflammatory complications associated with systemic inflammation. We summarize the evidence that support a role of a bidirectional pathogenic interaction between inflammation and metabolic disturbances in CVID. This include low levels and function of high-density lipoprotein (HDL), high levels of triglycerides (TG) and its major lipoprotein very low-density lipoprotein (VLDL), and an unfavorable fatty acid (FA) profile. The dysregulation of TG, VLDL and FA were linked to disturbed gut microbiota profile, and TG and VLDL levels were strongly associated with lipopolysaccharides (LPS), a marker of gut leakage in blood. Of note, the disturbed lipid profile in CVID did not include total cholesterol levels or high low-density lipoprotein levels. Furthermore, increased VLDL and TG levels in blood were not associated with diet, high body mass index and liver steatosis, suggesting a different phenotype than in patients with traditional cardiovascular risk such as metabolic syndrome. We hypothesize that these metabolic disturbances are linked to inflammation in a bidirectional manner with disturbed gut microbiota as a potential contributing factor

Tetradecylthioacetic Acid Increases Hepatic Mitochondrial β-Oxidation and Alters Fatty Acid Composition in a Mouse Model of Chronic Inflammation

The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced β-oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low-grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti-inflammatory fatty acid index in this group. We also observed an increase of mitochondrial β-oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ-butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels

Influence of conjugated linoleic acid (CLA) or tetradecylthioacetic acid (TTA) on growth, lipid composition, fatty acid metabolism and lipid gene expression of rainbow trout (Oncorhynchus mykiss L.)

Our objective was to test the hypotheses that conjugated linoleic acid (CLA) and/or tetradecylthioacetic acid (TTA) would have beneficial effects on the nutritional quality of rainbow trout (Oncorhynchus mykiss) through decreased lipid content of flesh or viscera, and increased levels of beneficial fatty acids including accumulation of CLA or TTA themselves. The specific aims of this study were to determine the effects of CLA and TTA on growth performance, lipid and fatty acid metabolism, and selected gene expression in commercial sized trout grown in seawater. Trout were fed for eight weeks on fish meal and fish oil diets containing either 0.5% or 1% CLA, or 0.5% TTA. The effects of the supplemented fatty acids on growth, feed efficiency, lipid contents, class compositions and fatty acid compositions of flesh and liver were determined, along with liver highly unsaturated fatty acid synthesis, activities of key enzymes of fatty acid oxidation in liver and muscle, and expression of carnitine palmitoyltransferase-I (CPT-I) and fatty acyl desaturase and elongase genes. Neither functional fatty acid had any effect on growth parameters, condition factor, viscero- and hepato-somatic indices or fillet colour, and there were no mortalities in any of the treatments. Dietary CLA, but not TTA, decreased the lipid content of liver, but neither fatty acid had any significant effect on lipid class compositions of liver and flesh. Both CLA and TTA were incorporated into tissue lipids, with higher percentages found in flesh compared to liver. In addition, production of hexaene fatty acid by liver microsomes was increased by dietary CLA or TTA, and both functional fatty acids increased the proportion of n-3 fatty acids in liver mainly due to increased 20:5n-3 and 22:6n-3. However, the expression of fatty acyl Δ6 desaturase was significantly lower in fish fed CLA or TTA, whereas the expression of PUFA elongase was increased, significantly so in fish fed 1% CLA. CPT-I activity was increased by TTA in liver and red muscle, and acyl CoA oxidase activity was increased by TTA in liver and CLA at the higher dietary inclusion level in red muscle. There was a clear trend for CPT-I expression to be increased in fish fed 0.5% CLA or TTA in all tissues although this was only significant in white muscle. The results showed that both CLA and TTA had effects on lipid metabolism that partly support the hypotheses tested. Although CLA or TTA did not enhance growth parameters, feed conversion or potential yield, nutritional quality could be enhanced, and sea-run trout fed CLA or TTA could be beneficial in the human diet through provision of bioactive fatty acids, with no detrimental effects on 20:5n-3 or 22:6n-3 levels