Liver Fatty Acid Binding Protein: Is it an early diagnostic and prognostic marker in liver damage?

Objective: The majority of the liver function tests are not specific to the liver. The histological liver damage begins before patients are diagnosed with cirrhosis and continues afterwards. Therefore, there is an increasing demand for early and specific markers that are correlated with liver damage. This study aims to investigate if serum and urinary liver fatty acid-binding protein (L-FABP) levels could be used as an early diagnostic marker of liver cirrhosis. Material and Methods: This cross-sectional study included 30 patients with compensated liver cirrhosis, 27 patients with decompensated liver cirrhosis, and 30 healthy controls. The patients and healthy controls were tested for serum and urinary L-FABP levels. Results: The serum and urinary L-FABP levels were higher in patients with cirrhosis than the healthy controls (both p<0.001). The cut-off value of serum and urinary L-FABP was computed as 721.78 ng/ml and 621.25 ng/ml, respectively. The sensitivity of serum and urinary L-FABP to detect cirrhosis at this cut-off was 99.8% and 98.9%. The specificity, positive predictive value, and negative predictive value of serum and urinary L-FABP at these cut-off levels were 100 %. There was no difference in terms of serum and urinary L-FABP between compensated and decompensated cirrhosis patients. Accordingly, no correlation was determined between serum/urinary L-FABP levels and cirrhosis complications. Conclusion: L-FABP increases in serum and urine in response to hepatocyte damage that can result in liver fibrosis. We demonstrated that patients with liver cirrhosis had high L-FABP levels. L-FABP may be used as a predictive non-invasive marker of cirrhosis as it can be detected before the clinical symptoms of liver damage.

No Evidence for Trade-Offs Between Lifespan, Fecundity, and Basal Metabolic Rate Mediated by Liver Fatty Acid Composition in Birds

The fatty acid composition of biological membranes has been hypothesised to be a key molecular adaptation associated with the evolution of metabolic rates, ageing, and life span – the basis of the membrane pacemaker hypothesis (MPH). MPH proposes that highly unsaturated membranes enhance cellular metabolic processes while being more prone to oxidative damage, thereby increasing the rates of metabolism and ageing. MPH could, therefore, provide a mechanistic explanation for trade-offs between longevity, fecundity, and metabolic rates, predicting that short-lived species with fast metabolic rates and higher fecundity would have greater levels of membrane unsaturation. However, previous comparative studies testing MPH provide mixed evidence regarding the direction of covariation between fatty acid unsaturation and life span or metabolic rate. Moreover, some empirical studies suggest that an n-3/n-6 PUFA ratio or the fatty acid chain length, rather than the overall unsaturation, could be the key traits coevolving with life span. In this study, we tested the coevolution of liver fatty acid composition with maximum life span, annual fecundity, and basal metabolic rate (BMR), using a recently published data set comprising liver fatty acid composition of 106 avian species. While statistically controlling for the confounding effects of body mass and phylogeny, we found no support for long life span evolving with low fatty acid unsaturation and only very weak support for fatty acid unsaturation acting as a pacemaker of BMR. Moreover, our analysis provided no evidence for the previously reported links between life span and n-3 PUFA/total PUFA or MUFA proportion. Our results rather suggest that long life span evolves with long-chain fatty acids irrespective of their degree of unsaturation as life span was positively associated with at least one long-chain fatty acid of each type (i.e., SFA, MUFA, n-6 PUFA, and n-3 PUFA). Importantly, maximum life span, annual fecundity, and BMR were associated with different fatty acids or fatty acid indices, indicating that longevity, fecundity, and BMR coevolve with different aspects of fatty acid composition. Therefore, in addition to posing significant challenges to MPH, our results imply that fatty acid composition does not pose an evolutionary constraint underpinning life-history trade-offs at the molecular level.

The Dietary Replacement of Soybean Oil by Canola Oil Does Not Prevent Liver Fatty Acid Accumulation and Liver Inflammation in Mice

A high-carbohydrate diet (HCD) is a well-established experimental model of accelerated liver fatty acid (FA) deposition and inflammation. In this study, we evaluated whether canola oil can prevent these physiopathological changes. We evaluated hepatic FA accumulation and inflammation in mice fed with a HCD (72.1% carbohydrates) and either canola oil (C group) or soybean oil (S group) as a lipid source for 0, 7, 14, 28, or 56 days. Liver FA compositions were analyzed by gas chromatography. The mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was measured as an indicator of lipogenesis. The mRNA expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, as mediators of liver inflammation, were also measured. The C group stored less n-6 polyunsaturated FAs (n-6 PUFAs) and had more intense lipid deposition of monounsaturated FAs (MUFAs), n-3 PUFAs, and total FAs. The C group also showed higher ACC1 expression. Moreover, on day 56, the C group showed higher expressions of the inflammatory genes F4/80, TNF-α, IL-1β, and IL-6, as well as the anti-inflammatory IL-10. In conclusion, a diet containing canola oil as a lipid source does not prevent the fatty acid accumulation and inflammation induced by a HCD.

The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism

Purpose. Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. Methods. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and then received CP775146 via intraperitoneal injection for 3 days. The content/morphology of the liver, serum lipid, and liver function was measured. The expression of genes related to lipolysis and synthesis in liver was detected by quantitative real-time PCR (qRT-PCR). Results. The safe dose of CP775146 was <0.3 mg/kg. CP775146 reduced the serum levels of liver enzymes, such as alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) and lipid metabolism-related biomarkers, including triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), and hepatic TG content, at a dosage of 0.1 mg/kg. HFD-induced pathological liver changes improved after CP775146 treatment. The expression of genes involved in liver fatty acid oxidation (acyl-coenzyme A dehydrogenase, long chain (Acadl), acyl-CoA oxidase 1 (Acox-1), carnitine palmitoyltransferase-1 (CPT-1), and enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh)) was upregulated in CP775146-treated mice. Furthermore, CP775146 induced the expression of thermogenesis genes (cell death-inducing DFFA-like effector a (Cidea), uncoupling protein 1 (Ucp1)) and lipolysis genes (hormone-sensitive lipase (Hsl), adipose tissue triglyceride lipase (Atgl)) in epididymal white adipose tissue (eWAT), activating browning and thermogenesis. Conclusion. CP775146 efficiently alleviates obesity-induced liver damage, prevents lipid accumulation by activating the liver fatty acid β-oxidation pathway, and regulates the expression of genes that control brown fat-like pathway in eWAT.