Hepatic lipid metabolism. Age-related changes in triglyceride metabolism.

Age-related changes in hepatic triglyceride formation have been described in developing rats. Triglyceride formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver homogenates and microsomal fractions derived from various age groups of animals. Triglyceride formation was most active in one-day-old rats and then decrease with age. The increase in triglyceride formation following birth was prevented by the administration of puromycin or by denying suckling. In addition, changes in plasma and hepatic triglyceride concentrations, were also determined as functions of age. These studies suggest that the age of the animal significantly influences triglyceride metabolism.     

Central administration of alpha-melanocyte-stimulating hormone changes lipid metabolism in chicks

Alpha-melanocyte-stimulating hormone (MSH) is well known as an anorexigenic peptide in the brain of mammals. In addition to this, brain alpha-MSH enhances heat production (HP), indicating that the peptide acts as a catabolic factor in the regulation of energy metabolism. The anorexigenic effect of alpha-MSH is also observed in chicks (Gallus gallus), but no information has been available for its effect on HP. The present study was performed to examine whether intracerebroventricular (ICV) injection of alpha-MSH increases HP in chicks. The injection of alpha-MSH (10 and 100 pmol) did not affect oxygen consumption, carbon dioxide production and HP during the 1 h post-injection period. This result was supported by another result that ICV injection of alpha-MSH did not affect locomotion activity in chicks. In contrast, the respiratory quotient was significantly lowered by the ICV injection of MSH. We also found that alpha-MSH significantly increased plasma non-esterified fatty acid concentrations. In summary, brain alpha-MSH appears to exert generally catabolic effects on lipid metabolism in the chick, but does not appear to be involved in the regulation of HP.     

Gibberellin-induced changes in glycolysis and in lipid metabolism of wheat leaves

V listech p?enice, pěstované 4 a? 10 dní v roztoku kys. giberelové (10–20 p.p.m.) bylo chromatografickou analysou zji?têno zvý?ení hladiny fruktoso-1,6-difosfátu v poměru ke kyselině 3-fosfoglycerové a fosfoenolpyrohroznové a kyseliny 3-fosfo-glycerové v poměru k dosud neidentifikovanému fosfátu. Tyto změny byly nalezeny za r?zných světelných re?im?, je? p?edcházely extrakci fosfát? z list?. Na základě těchto údaj? byl se z?etelem k výsledk?m d?ívěj?ích pokus? (Lu?tinec, Pokorná aR??i?ka 1962) vysloven p?edpoklad o interakei mezi glykolysou a reakcemi spot?ebovávajícími její meziprodukty pro synthesu lipid? jako?to o zp?sobu, kterým se m??e měnit p?sobením kyseliny giberelové hladina analysovaných fosfát? v listech. Za ú?elem ově?ení jeho správnosti byla sledována inkorporace 1-¹⁴C- a 6-¹⁴C-glukosy do lipid?, fosfolipid? (jejich? ho?e?natá s?l je nerozpustná v acetonu), CO₂ a nelipidické frakce list?. Ukázalo se, ?e inkorporace 1-¹⁴C do lipidických frakcí rostlin pěstovaných 3 a? 7 dní v roztoku kys. giberelové je nápadně sní?ena ve srovnání s inkorporací 6-¹⁴C. Poměr radioaktivit C₆∶C₁ byl v lipidech zna?ně zvý?en, také t?íhodinovým p?sobením kyseliny giberelové (10 a 50 p.p.m.) na listy p?i jejich inkubaci s glukosou-¹⁴C. Vzhledem k tomu, ?e mno?ství látek extrahovatelných etherem je v listech pokusných rostlin stejné jako u kontroly a ?e inkorporace 1-C do lipid? je v ?adě p?ípad? u kontrolních rostlin zna?ně vy??í ne? inkorporace 6-C, je nutno uva?ovat o ú?inku kyseliny giberelové na rychlost výměny uhlíkových atom? mezi lipidy a produkty katabolismu glukosy.     

Intracerebroventricular injection of glucagon-like peptide-1 changes lipid metabolism in chicks

Glucagon-like peptide-1 (GLP-1), derived from proglucagon, is thought to act as a negative regulator of energy homeostasis in mammals, since intracerebroventricular (ICV) injection of GLP-1 inhibits feeding behavior and enhances energy expenditure. The anorexigenic effect of GLP-1 is also observed in chicks, but whether brain GLP-1 enhances energy expenditure has not been investigated. The aim of the present study was to clarify the effect of ICV injection of GLP-1 on energy expenditure as well as metabolic changes in chicks. The injection of GLP-1 did not affect energy expenditure calculated from oxygen consumption and carbon dioxide production. On the other hand, the injection of GLP-1 significantly decreased respiratory quotient, suggesting that brain GLP-1 shifted the use of energy sources from carbohydrates to lipids. In support of this, ICV injection of GLP-1 increased plasma non-esterified fatty acid concentration while plasma glucose concentration was decreased. In conclusion, GLP-1 appears to act in the brain as a metabolic modulator rather than as a regulator of total energy expenditure in chicks.     

Upstream regulators of apoptosis mediates methionine-induced changes of lipid metabolism

Although the role of methionine (Met), as precursor for l-carnitine synthesis, in the regulation of lipid metabolism has been explored. Met seems to have tissue- and species-specific regulatory effect on lipid metabolism, implying that the mechanisms in Met regulation of lipid metabolism is complex and may involve the upstream regulatory pathway of lipid metabolism. The present study was performed to determine the mechanism of apoptosis signaling pathways mediating Met-induced changes of hepatic lipid deposition and metabolism in fish, and compare the differences of the mechanisms between the fish and mammals. By iTRAQ-based quantitative proteome analyses, we found that both dietary Met deficiency and excess evoked apoptosis signaling pathways, increased hepatic lipid deposition and caused aberrant hepatic lipid metabolism of yellow catfish Pelteobagrus fulvidraco. Using primary hepatocytes from P. fulvidraco, inhibition of caspase by Z-VAD-FMK blocked the apoptotic signaling pathways with a concomitant reversal of Met deficiency- and excess-induced increase of lipid deposition, indicating that apoptosis involved the Met-mediated changes of hepatic lipid metabolism. Moreover, we explored the roles of three upstream apoptotic signaling pathways (PI3K/AKT-TOR pathway, cAMP/PKA/CREB pathway and LKB1/AMPK-FOXO pathway) influencing hepatic lipid metabolism of P. fulvidraco. The three upstream pathways participated in apoptosis mediating Met-induced changes of lipid metabolism in P. fulvidraco. At last, HepG2 cell line was used to compare the similarities of mechanisms in apoptosis mediating Met-induced changes of lipid metabolism between fish and mammals. Although several slight differences existed, apoptosis mediated the Met-induced changes of lipid metabolism between fish and mammals. The present study reveals novel apoptosis-relevant signal transduction axis which mediates the Met-induced changes of lipid metabolism, which will help understand the mechanistic link between apoptosis and lipid metabolism, and highlight the importance of the evolutionary conservative apoptosis signaling axis in regulating Met–induced changes of hepatic lipid metabolism.     

Comparison of the changes in lipid metabolism between hepatoma-bearing and lipopolysaccharide-treated rats

To elucidate the mechanism for hyperlipidemia in the hepatoma-bearing state, changes in some parameters related to the lipid metabolism and serum tumor necrosis factor-alpha (TNF-alpha) level were examined in Donryu rats that had been subcutaneously implanted with an ascites hepatoma cell line of AH109A. These parameters were also examined in rats that had been given a single injection of lipopolysaccharide (LPS), a model for acute infection with TNF-alpha secretion into the blood circulation. The serum triglyceride and total cholesterol (Ch) levels were significantly higher in both the hepatoma-implanted and LPS-injected rats than in normal rats. The level of adipose tissue lipoprotein lipase was decreased by hepatoma implantation and LPS injection, while the hormone-sensitive lipase activity was increased by the same treatments. Fatty acid (FA) oxidation and Ch synthesis were also stimulated by both treatments. The serum TNF-alpha level was noticably elevated by hepatoma implantation and greatly by the LPS injection. This LPS injection increased hepatic FA synthesis. The serum high-density lipoprotein Ch level and hepatic Ch 7alpha-hydroxylase activity were not changed by the LPS injection. Hepatoma implantation led to hyperlipidemia and elevated the serum TNF-alpha level, as did the LPS injection.     

Time-dependent changes in lipid metabolism in mice with methionine choline deficiency-induced fatty liver disease

Methionine and choline-deficient diet (MCD)-induced fatty liver is one of the best-studied animal models of fatty liver disease. The present study was performed to clarify the relative contributions of individual lipid metabolic pathways to the pathogenesis of MCD-induced fatty liver. Hepatic lipogenesis mediated by the sterol regulatory element-binding protein (SREBP-1c) was increased at 1 week, but not at 6 weeks, of MCD feeding. On the other hand, ¹⁴C-palmitate oxidation did not change at 1 week, but significantly decreased at 6 weeks. This decrease was associated with increased expression of fatty acid translocase, a key enzyme involved in fatty acid uptake. Expression of endoplasmic reticulum stress markers was increased in mice given MCD for both 1 and 6 weeks. These findings suggest the presence of time-dependent differences in lipid metabolism in MCD-induced fatty liver disease: SREBP-1c-mediated lipogenesis is important in the early stages of fatty liver disease, whereas increased fatty acid uptake and decreased fatty acid oxidation become more important in the later stages.     

Dysregulated lipid metabolism in cancer

Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.     

Maternal lipid metabolism and placental lipid transfer

During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may accumulate in maternal fat depots and become available for placental transfer during late pregnancy, when the fetal growth rate is maximal and fetal requirements for LC-PUFAs are greatly enhanced. During this late part of gestation, enhanced lipolytic activity in adipose tissue contributes to the development of maternal hyperlipidaemia; there is an increase in plasma triacylglycerol concentrations, with smaller rises in phospholipid and cholesterol concentrations. Besides the increase in plasma very-low-density lipoprotein, there is a proportional enrichment of triacylglycerols in both low-density lipoproteins and high-density lipoproteins. These lipoproteins transport LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the placenta allows their placental uptake, where they are hydrolysed by lipoprotein lipase, phospholipase A(2) and intracellular lipase. The fatty acids that are released can be metabolized and diffuse into the fetal plasma. Although present in smaller proportions, maternal plasma non-esterified fatty acids are also a source of LC-PUFA for the fetus, their placental transfer being facilitated by the presence of a membrane fatty acid-binding protein. There is very little placental transfer of glycerol, whereas the transfer of ketone bodies may become quantitatively important under conditions of maternal hyperketonaemia, such as during fasting, a high-fat diet or diabetes. The demands for cholesterol in the fetus are high, but whereas maternal cholesterol substantially contributes to fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather than cholesterol transfer from maternal lipoproteins seems to be the main mechanism for satisfying fetal requirements during late pregnancy.     

Effect of essentiale on pulmonary edema and changes in the lipid metabolism during adrenaline administration

The experiments on white rats have confirmed that the development of lung edema following epinephrine infusion is characterized by considerable changes in phospholipid and cholesterol blood and lung metabolism. Essentiale preinjection prevented the decrease in phospholipid lung content and blood plasma cholesterol, which was accompanied by less prominent lung edema.     

Differentiation of strains of varicella-zoster virus by changes in neutral lipid metabolism in infected cells.

Eleven isolates of varicella-zoster virus were tested for their effects on the incorporation of [14C]acetate into lipids in infected human embryonic lung cells. By relative percent, all virus isolates demonstrated a shift from polar lipid synthesis to neutral lipid, especially triglyceride, synthesis. By data expressed as counts per minute per microgram of protein, the VZV strains could be separated into two groups: those strains which depressed lipid synthesis and those strains which did not depress, and may even have stimulated, lipid, especially triglyceride, synthesis. These results may be useful in understanding the development of lipid changes seen in children affected with Reye's syndrome following chickenpox.     

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (−25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene–nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0385-7) contains supplementary material, which is available to authorized users.