Lipid Metabolism

Perilipin 2, also known as Adipose differentiation-relation protein or PLIN2, is a lipid droplet-binding protein present in almost every tissue. The absence of PLIN2 upregulates hepatic very low-density lipoprotein secretion, relieves hepatosteatosis, and improves whole body insulin resistance in mice. Despite of the importance in mediating lipid metabolism, the regulation of PLIN2 itself remains largely unknown. Previous reports have shown that X-box binding protein 1 (XBP1) is an important regulator of lipogenesis. XBP1 is a transcription factor that recognizes and binds to a consensus sequence, 5’-TGACGTGG-3’. Interestingly, when we looked through the promoter region of mouse Plin2 gene, we found that the consensus sequence is present in the Plin2 promoter. Therefore, we hypothesize that XBP1 might directly bind to Plin2 promoter and regulate the Plin2 expression. To test our hypothesis, we will perform the luciferase assay to examine whether the Plin2 promoter activity is regulated by XBP1. We first designed forward and reverse PCR primers, which include BglII and BamHI restriction enzyme sites respectively, to amplify the Plin2 promoter region (from -1100 to +40). We performed PCR and cloned the Plin2 promoter to a TA vector. The TA vector was then sequenced to exclude any point mutations. After sequencing, we sub cloned the Plin2 promoter into a vector containing a luciferase reporter. In the future, we will transfect 293T, a human embryonic kidney cell line, with the Plin2 promoter-luciferase vector we generated. We will compare the Plin2 promoter activity by measuring the luminescence in the presence or absence of XBP1

Lipid Metabolism and Comparative Genomics

Unilever asked the Study Group to focus on two problems. The first concerned dysregulated lipid metabolism which is a feature of many diseases including metabolic syndrome, obesity and coronary heart disease. The Study Group was asked to develop a model of the kinetics of lipoprotein metabolism between healthy and obese states incorporating the activities of key enzymes. The second concerned the use of comparative genomics in understanding and comparing metabolic networks in bacterium. Comparative genomics is a method to make inferences on the genome of a new organism using information of a previously charaterised organism. The first mathematical question is how one would quantify such a metabolic map in a statistical sense, in particular, where there are different levels of confidence for presense of different parts of the map. The next and most important question is how one can design a measurement strategy to maximise the confidence in the accuracy of the metabolic map

Different Effects of Maternal Low-Isoflavone Soy Protein and Genistein Consumption on Hepatic Lipid Metabolism of 21-Day-Old Male Rat Offspring.

Amino acid composition and isoflavone are alleged contributors to the beneficial effects of soy protein isolate (SPI) on lipid metabolism. Therefore, we investigated the contributing component(s) of SPI in a maternal diet to the regulation of lipid metabolism in offspring. We also determined serum parameters in dams to investigate specific maternal cues that might be responsible for this regulation. Female rats were fed either a casein (CAS), a low-isoflavone SPI, or a casein plus genistein (GEN, 250 mg/kg) diet for two weeks before mating, as well as during pregnancy and lactation. Male offspring (CAS, SPI and GEN groups) were studied 21 days after birth. The SPI group had lower serum triglyceride levels than the other groups. Serum cholesterol was reduced in both the SPI and GEN groups compared with the CAS group. Expressions of target genes of peroxisome proliferator-activated receptor α were altered in the SPI group. Serum aromatic amino acid levels in dams were associated with serum triglyceride in offspring. In conclusion, the maternal consumption of a low-isoflavone SPI diet or a casein diet containing genistein has different effects on the lipid metabolism of their offspring; however, more profound effects were observed in the SPI group. Therefore, the altered lipid metabolism of offspring may be attributed to amino acid composition in maternal dietary protein sources

Getting a handle on lipid droplets: Insights into ER-lipid droplet tethering.

Lipid droplets (LDs) are hubs for lipid metabolism that form membrane contact sites with multiple organelles. In this issue, Hariri et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808119) reveal the functions of Mdm1-mediated endoplasmic reticulum (ER)-LD tethering in yeast and Datta et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808133) identify a role for the Mdm1 orthologue, Snx14, as an ER-LD tether that regulates lipid metabolism in human cells

Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Investigation of lipid metabolism dysregulation and the effects on immune microenvironments in pan-cancer using multiple omics data.

BACKGROUND: Lipid metabolism reprogramming is a hallmark for tumor which contributes to tumorigenesis and progression, but the commonality and difference of lipid metabolism among pan-cancer is not fully investigated. Increasing evidences suggest that the alterations in tumor metabolism, including metabolite abundance and accumulation of metabolic products, lead to local immunosuppression in the tumor microenvironment. An integrated analysis of lipid metabolism in cancers from different tissues using multiple omics data may provide novel insight into the understanding of tumorigenesis and progression. RESULTS: Through systematic analysis of the multiple omics data from TCGA, we found that the most-widely altered lipid metabolism pathways in pan-cancer are fatty acid metabolism, arachidonic acid metabolism, cholesterol metabolism and PPAR signaling. Gene expression profiles of fatty acid metabolism show commonalities across pan-cancer, while the alteration in cholesterol metabolism and arachidonic acid metabolism differ with tissue origin, suggesting tissue specific lipid metabolism features in different tumor types. An integrated analysis of gene expression, DNA methylation and mutations revealed factors that regulate gene expression, including the differentially methylated sites and mutations of the lipid genes, as well as mutation and differential expression of the up-stream transcription factors for the lipid metabolism pathways. Correlation analysis of the proportion of immune cells in the tumor microenvironment and the expression of lipid metabolism genes revealed immune-related differentially expressed lipid metabolic genes, indicating the potential crosstalk between lipid metabolism and immune response. Genes related to lipid metabolism and immune response that are associated with poor prognosis were discovered including HMGCS2, GPX2 and CD36, which may provide clues for tumor biomarkers or therapeutic targets. CONCLUSIONS: Our study provides an integrated analysis of lipid metabolism in pan-cancer, highlights the perturbation of key metabolism processes in tumorigenesis and clarificates the regulation mechanism of abnormal lipid metabolism and effects of lipid metabolism on tumor immune microenvironment. This study also provides new clues for biomarkers or therapeutic targets of lipid metabolism in tumors

Influence of Dietary Fats and Carbohydrates on Lipid Metabolism in Male and Female Rats

Effects of dietary fats and carbohydrates on lipid metabolism in rats were studied. Male and female 4-week-old rats were divided into 8 groups and fed 4 fat-carbohydrate combinations (beef tallow or safflower oil, each with either sucrose or rice starch). After 4 weeks, animals were killed by exsanguination through the abdominal aorta and livers were removed. Plasma and liver cholesterol and phospholipids were determined qualitatively and quantitatively. Liver moisture, protein, and lipid and the fatty acid composition of the total liver lipid were determined quantitatively. Variations in growth, food efficiency, and lipid metabolism, particularly as manifested by the fatty acid composition of the liver lipid, were apparent between males and females and among groups of each sex as a result of dietary treatment

MicroRNAs and Lipid Metabolism

Lipid metabolism is closely related to the occurrence and development of various diseases, and microRNAs, as important post-transcriptional regulatory factors, are involved in various biological processes of adipocyte differentiation and lipid metabolism to regulate lipid metabolism. In this paper, the effects of miRNAs on adipocyte differentiation, lipid synthesis, decomposition and transport reported in recent years are reviewed, with the hope of promoting the mechanism of microRNA in lipid metabolism disorders