Human Lipid Metabolism Research Articles

From the Editor’s Desk...

From the Editor’s Desk...

The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence.

Approximately 25–50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.

Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids - A longitudinal study over 10 years

BackgroundAssociations between per- and polyfluoroalkyl substances (PFAS), mainly PFOS and PFOA, and increased blood lipids have been reported primarily from cross-sectional studies. The aim of the present study was to investigate associations between multiple PFAS and blood lipids in a longitudinal fashion. MethodsA total of 864 men and women aged 70 years and free from lipid medication were included from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study from Uppsala Sweden, 614 and 404 of those were reinvestigated at age 75 and 80. At all three occasions, eight PFAS were measured in plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were also measured in plasma at all three occasions. Mixed-effects linear regression models were used to examine the relationship between the changes in PFAS levels and changes in lipid levels. ResultsChanges in plasma levels of six out of the eight investigated PFAS were positively associated with changes in plasma lipids after adjustment for sex, change in body mass index (BMI), smoking, physical activity, statin use (age was the same in all subjects), and correction for multiple testing. For example, changes in perfluorodecanoic acid (PFDA) were positively associated with the changes in total cholesterol (β: 0.23, 95% confidence interval (CI): 0.14 to 0.32), triglycerides (β: 0.08, 95% CI: 0.04–0.12) and HDL-cholesterol (β: 0.08, 95% CI: 0.04–0.11). ConclusionIn this longitudinal study with three measurements over 10 years of both plasma PFAS and lipids, changes in six out of the eight investigated PFAS were positively associated with changes in plasma lipids, giving further support for a role of PFAS exposure in human lipid metabolism.

Exploiting three-dimensional human hepatic constructs to investigate the impact of rs174537 on fatty acid metabolism.

The Modern Western Diet has been associated with the rise in metabolic and inflammatory diseases, including obesity, diabetes, and cardiovascular disease. This has been attributed, in part, to the increase in dietary omega-6 polyunsaturated fatty acid (PUFA) consumption, specifically linoleic acid (LA), arachidonic acid (ARA), and their subsequent metabolism to pro-inflammatory metabolites which may be driving human disease. Conversion of dietary LA to ARA is regulated by genetic variants near and within the fatty acid desaturase (FADS) haplotype block, most notably single nucleotide polymorphism rs174537 is strongly associated with FADS1 activity and expression. This variant and others within high linkage disequilibrium may potentially explain the diversity in both diet and inflammatory mediators that drive chronic inflammatory disease in human populations. Mechanistic exploration into this phenomenon using human hepatocytes is limited by current two-dimensional culture models that poorly replicate in vivo functionality. Therefore, we aimed to develop and characterize a three-dimensional hepatic construct for the study of human PUFA metabolism. Primary human hepatocytes cultured in 3D hydrogels were characterized for their capacity to represent basic lipid processing functions, including lipid esterification, de novo lipogenesis, and cholesterol efflux. They were then exposed to control and LA-enriched media and reproducibly displayed allele-specific metabolic activity of FADS1, based on genotype at rs174537. Hepatocytes derived from individuals homozygous with the minor allele at rs174537 (i.e., TT) displayed the slowest metabolic conversion of LA to ARA and significantly reduced FADS1 and FADS2 expression. These results support the feasibility of using 3D human hepatic cultures for the study of human PUFA and lipid metabolism and relevant gene-diet interactions, thereby enabling future nutrition targets in humans.

CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions.

The aim of this study was to investigate whether CD74 levels in atherosclerotic lesions are associated with inflammation, apoptosis, plaque severity, and clinical symptoms among patients with carotid atherosclerosis. We further studied whether CD74 expression is associated with apoptosis in macrophages induced by 7ketocholesterol (7keto). Sixty-one carotid samples (39 males and 22 females) were immunostained with macrophages, smooth muscle cells, CD74, ferritin, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), and thrombin receptors. Double immunocytochemistry of CD74 and caspase 3 or CD74 and Annexin V was performed on THP-1 macrophages exposed to 7keto. In human carotid plaques, CD74 expression is lesion-dependently increased and is associated with necrotic core formation and plaque rupture, clinical symptoms, macrophage apoptosis, ferritin, and thrombin receptors. CD74 levels were inversely correlated to high-density lipoproteins and statin treatment, and positively correlated to triglycerides. In THP-1 macrophages, 7keto induced a significant increase in levels of CD74, ferritin, and apoptotic cell death. This study suggests that CD74 in apoptotic macrophages is linked to inflammation and thrombosis in progression of human atherosclerotic plaques, lipid metabolism, and clinical manifestation in atherosclerosis. Surface CD74 in apoptotic macrophages and ferritin production induced by oxidized lipids may contribute to inflammation and plaque vulnerability in atherosclerosis.

The Effect of Fasting on Human Metabolism and Psychological Health.

Fasting is a prevalent approach to weight loss and is a feasible method for treating some diseases, such as type 2 diabetes. Meanwhile, the effects of intermittent fasting on health, aging, and disease process are hot issues and are of concern by researchers of multiple areas, even the public. This article introduces the effects of fasting on human lipid metabolism, glucose metabolism, protein metabolism, and neuroendocrine metabolism; demonstrates the metabolic conversion caused by fasting; and describes the effects of fasting on human psychological health, the relationship between mood regulation and glucose, and the emotional enhancing effect induced by fasting.

Two new ɑ-pyrone derivatives from the endophytic Diaporthe sp. ECN371.

Diaportholides A (1) and B (2), two polyketides with ɑ-pyrone moieties, were isolated from the cultures of an endophytic Diaporthe sp. ECN371 isolated from Orixa japonica, together with four known polyketides, phomopsolide B (3), phomopsolidones A (4) and B (5), and 5-[(1R)-1-hydroxyethyl]-γ-oxo-2-furanbutanoic acid (6). The structures of 1 and 2 were determined by extensive analysis of NMR and MS spectroscopic data. Furthermore, the structure of 2 was confirmed by analyzing the single-crystal X-ray diffraction data. The luciferase reporter gene assay revealed that among all isolated compounds (1-6), 3, a known ɑ-pyrone derivative, exhibited agonistic activity against the peroxisome proliferator-activated receptor ɑ, which is an important regulator of lipid metabolism in humans.

A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans.

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.

Correlation Studies between Leptin, Glucose and Insulin in Pre and Postmenopausal Saudi

Leptin act as a regulator of cellular energy metabolism but its role in lipid metabolism in humans is still unclear. Relation between leptin and plasma lipids in Saudi females was evaluated in this study. 126 females with age ranging from 18 to 75 years were recruited and grouped into premenopausal and postmenopausal females and then in lean, normal weight, overweight, and obese on the basis of their BMI values. The serum samples were assessed for Leptin, Cholesterol, triglycerides, High-density lipoproteins (HDL-C), Low-density lipoproteins (LDL-C), insulin and glucose. Significant increase in glucose, triglycerides and leptin was associated with increase weight. Insulin level was found to be significantly highest in overweight group. Cholesterol, LDL-C was found to increase with increase weight while HDL-C was decreased with increased weight. Leptin, triglycerides and glucose were significantly higher (P<0.05) in the postmenopausal females as compared to the premenopausal group. Remarkable increase of cholesterol and glucose was found in postmenopausal female while HDL-C, LDL-C and insulin were slightly decreased in postmenopausal females. High serum leptin levels can act as the risk factor for diabetes in obese and postmenopausal female. Regular monitoring of total leptin at pre-menopause stage could help in managing some life-threatening condition related to obesity in old age.

Low blood levels of high-density lipoprotein (HDL) cholesterol are positively associated with cancer

PurposeThere is a growing body of evidence suggesting a decisive involvement of the human lipid metabolism in cancer development. However, clinical data on the association between blood triglyceride or cholesterol levels including the cholesterol transporters high-density and low-density lipoproteins (LDL, HDL) and cancer incidence have remained inconclusive. Here, we investigated the association between blood triglyceride as well as total, LDL and HDL cholesterol levels and cancer among outpatients from Germany.Methods61,936 patients with available blood lipid values were identified from the IQVIA Disease Analyzer database and followed up between 2005 and 2019. Multivariable logistic regression models were used to study the association between lipid values and cancer.ResultsThe probability of cancer was significantly lower among patients with elevated total cholesterol concentrations and higher in patients with decreased HDL serum levels. In contrast, serum concentrations of LDL and triglycerides had no impact on cancer risk. In cancer site-stratified analyses, we observed a trend towards higher rates of cancers from digestive organs, breast, skin cancer, urinary tract and cancers from lymphoid and hematopoietic tissue in patients with HDL values < 35 mg/dl, while a negative association between total cholesterol > 250 mg/dl and respiratory organ as well as urinary tract cancers was observed.ConclusionOur data strongly support the hypothesis that serum-specific lipid profiles are positively associated with cancer.

Dietary fatty acid metabolism: New insights into the similarities of lipid metabolism in humans and hamsters

Hamsters have been long accepted as animal models to study the lipid metabolism in humans. However, very few scientific works described in detail the fatty acid (FA) composition of plasma and erythrocytes in hamsters in relation to their dietary intake, and none work was found comparing them with that described in humans. Therefore, a study was carried out to compare the effect of ingesting olive oil or dairy fat, as part of an equilibrated diet in healthy subjects, on plasma and erythrocytes FA composition. More than 40 FA were detected in samples of both species. It was demonstrated that plasma total FA (TFA) concentration and FA profiles are similar in humans and hamsters. In both species linoleic, oleic and palmitic acids are the main FA and accounted for the 70% of TFA. Differences found between species can be explained by differences in the dietary intake and differences in the proportion of triglycerides, cholesteryl esters and phospholipid fractions in plasma of both species. Changes in dietary FA intake causes similar changes in FA concentration in the plasma of both species and can be explained by the same metabolic processes. The erythrocyte FA profile differs more between the two species. Moreover, unlike humans, the FA profile of hamster erythrocytes is more sensitive to changes in dietary FA than that of plasma.

Identifying active xenobiotics in humans by use of a suspect screening technique coupled with lipidomic analysis.

Lipidomic analysis has been proven to be a powerful technique to explore the underlying associations between xenobiotics and health status of organisms. Here, we established a strategy that combined the lipidomic analysis with high-throughput suspect contaminant screening technique with an aim to efficiently identify active xenobiotics in humans. Firstly, in the light of single liquid phase equilibrium of chloroform-methanol-water (15:14:2, v/v/v), we developed an efficient method that was able to simultaneously extract both polar and nonpolar lipids in serum samples. By use of this method, targeted and non-targeted lipid analyses were conducted for n=120 serum samples collected from Wuxi city, China. Secondly, we established a suspect database containing 1450 contaminants that have been previously reported in human samples, and contaminants in this database were screened in the same batch of serum samples by use of high-resolution mass spectrometry (HR-MS). Thirdly, the underlying associations between suspect contaminants and lipids were explored and discussed, and we observed that levels of some lipids were statistically correlated with concentrations of numerous contaminants. Among these active contaminants, 23 ones were identified on the basis of HR MS1 and MS2 characteristics, and these contaminants belonged to the classes of phthalates, phenols, parabens, or perfluorinated compounds (PFCs). Three active xenobiotics were fully validated by comparison with authentic standards, and they were perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and diethyl phthalate (DEP). There were statistically significant changes in levels of triglyceride (TG), lysophosphocholine (LPC), and sphingomyelin (SM) as peak areas of xenobiotics increase. We also observed that, among target lipid molecules, 18:0 lysophosphatidylethanolamine (LPE(18:0)) was very sensitive, and this lipid responded to exposure of various contaminants. Our present study provides novel knowledge on potential alteration of lipid metabolism in humans following exposure to xenobiotics, and provides an efficient strategy for efficiently identifying active xenobiotics in humans.

CS6253 ABCA1 agonist in cynomolgus monkeys increases APOA‐I subspecies PREβ‐HDL and lowers Aβ42 and Aβ40 in cerebrospinal fluid

AbstractBackgroundThen main genetic late‐onset Alzheimer’s disease (AD) risk factor, apolipoprotein E (APOE) ε4 genotype is characterized by the apoE4 protein having impaired interaction with astrocyte’s ATP‐binding cassette transporter A1 (ABCA1) resulting in; (1) poor cholesterol efflux (Bielicki 2016) to apoE and reduced lipid transport to cells in brain, (2) build‐up of residual cholesterol in lipid rafts, impeding astrocyte function (Rawat 2019), and (3) increased neuron cell death (Voskuhl 2018). ApoE as opposed to most other apolipoproteins does not cross the blood brain barrier (BBB). It has been suggested that the apoA‐I subspecies preβ‐HDL effectively crosses the BBB where it can compensate for ApoE4’s impaired interaction with ABCA1. We hypothesized that the ABCA1 agonist CS6253 would generate preβ‐HDL in plasma and decrease AD risk factors in brain including Aβ42.Method In vitro: CS6253 was incubated with human plasma (Figure, A‐B) and generation of preβ‐HDL assessed by 2D electrophoreses using a.b. to apoA‐I and CS6253 generating EC50 values. In vivo: Cynomolgus monkeys (cynos) have 93% homology with human apoE, lipid and amyloid metabolism similar to humans making them representative models for humans. In cynos; (1) CS6253 single dose 25 mg/kg iv was administered (n=2) and plasma collected for preβ‐HDL analysis by ELISA (Daichii a.b.) (Figure, C); (2) CS6253 multiple dose 0 (control), 75, 150 and 225 mg/kg iv (n=2/sex/group) 5 times was administered over 10 days and plasma collected serially for preβ‐HDL analysis (Figure, D). CSF and plasma were collected before treatment and 6 hours after the 5th/last dosing and Aβ42 and 40 analyzed by SIMOA.ResultCS6253 increased preβ‐HDL in vitro in human plasma and in vivo in cynos, see Figure. In cynos CS6253 decreased Aβ42 and Aβ40 concentration in CSF following dose‐response pattern.ConclusionThe CS6253 ABCA1 agonist transiently increases plasma preβ‐HDL and reduces CSF concentrations of Aβ42 and Aβ40. The Aβ reduction is consistent with apoE targeted replacement mice models studies where CS6253 reduced Aβ42, prevented AD brain pathology and improved cognition. Studies in human APOE ε4 carriers with and without AD are needed to corroborate these findings and to investigate the therapeutic potential of CS6253 or similar compounds.

Circulating bile acids concentration is predictive of coronary artery disease in human

Synthetized by the liver and metabolized by the gut microbiota, BA are involved in metabolic liver diseases that are associated with cardiovascular disorders. Animal models of atheroma documented a powerful anti-atherosclerotic effect of bile acids (BA). This prospective study examined whether variations in circulating BA are predictive of coronary artery disease (CAD) in human. Consecutive patients undergoing coronary angiography were enrolled. Circulating and fecal BA were measured by high pressure liquid chromatography and tandem mass spectrometry. Of 406 screened patients, 80 were prospectively included and divided in two groups with (n = 45) and without (n = 35) CAD. The mean serum concentration of total BA was twice lower in patients with, versus without CAD (P = 0.005). Adjusted for gender and age, this decrease was an independent predictor of CAD. In a subgroup of 17 patients, statin therapy doubled the serum BA concentration. Decreased serum concentrations of BA were predictors of CAD in humans. A subgroup analysis showed a possible correction by statins. With respect to the anti-atherosclerotic effect of BA in animal models, and their role in human lipid metabolism, this study describe a new metabolic disturbance associated to CAD in human.

Lipidomic profiling reveals lipid regulation by a novel LSD1 inhibitor treatment

Lipid metabolic alterations are associated with cancer progression. Lysine-specific demethylase 1 (LSD1) plays a crucial role in cancer and has become a promising target for cancer therapy. However, the effect of LSD1 on lipid metabolism remains unclear. In the present study, we used a LC-MS/MS-based lipidomics approach to investigate the impact of LSD1 on cancer cell lipid metabolism using ZY0511, a specific LSD1 inhibitor developed by our group as a specific probe. ZY0511 profoundly modified the human colorectal and cervical cancer cell lipid metabolism. A total of 256 differential metabolites were identified in HeLa cells, and 218 differential metabolites were identified in HCT116 cells, respectively. Among these lipid metabolites, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine and sphingomyelin (SM) were downregulated by ZY0511. In contrast, ceramide (Cer) and a small portion of glycerophospholipids such as phosphatidylinositol and phosphatidylethanolamine were upregulated by ZY0511. These results revealed a disturbance in sphingolipids (SPs) and glycerophospholipids, which may be correlated with the progression of cancer. Furthermore, a marked increase in Cer and prominent decrease in SM were consistent with the upregulated expression of key enzymes in the Cer synthesis process including de novo synthesis, hydrolysis of SM and the salvage pathway after ZY0511 exposure. In conclusion, our research reveals a link between LSD1 and lipid metabolism in cancer cells, offering more comprehensive evidence for the application of LSD1 inhibitors for cancer therapy. The underlying mechanisms of how the LSD1 inhibitor regulates lipid metabolism warrant further investigation.

Theaflavin Promotes Mitochondrial Abundance and Glucose Absorption in Myotubes by Activating the CaMKK2-AMPK Signal Axis via Calcium-Ion Influx.

Drinking tea has been proven to have a positive biological effect in regulating human glucose and lipid metabolism and preventing type 2 diabetes (T2D). Skeletal muscle (SkM) is responsible for 70% of the sugar metabolism in the human body, and its dysfunction is an important factor leading to the development of obesity, T2D, and muscle diseases. As one of the four known theaflavins (TFs) in black tea, the biological role of theaflavin (TF1) in regulating SkM metabolism has not been reported. In this study, mature myotubes induced by C2C12 cells in vitro were used as models. The results showed that TF1 (20 μM) promoted mitochondrial abundance and glucose absorption in myotubes by activating the CaMKK2-AMPK signaling axis via Ca2+ influx. Moreover, it promoted the expression of slow muscle fiber marker genes (Myh7, Myl2, Tnnt1, and Tnnc1) and PGC-1α/SIRT1, as well as enhanced the oxidative phosphorylation capacity of myotubes. In conclusion, this study preliminarily clarified the potential role of TF1 in regulating SkM glucose absorption as well as promoting SkM mitochondrial biosynthesis and slow muscle fiber formation. It has potential research and application values for the prevention/alleviation of SkM-related T2D and Ca2+-related skeletal muscle diseases through diet.

DGAT2 stability is increased in response to DGAT1 inhibition in gene edited HepG2 cells

In eukaryotic organisms, two unrelated acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2, catalyze the final step of the triacylglycerol biosynthetic pathway. Both enzymes are highly expressed in lipogenic tissues, such as adipose tissue, small intestine and the liver. DGAT2 has a prominent role in hepatocyte lipid metabolism synthesizing triacylglycerols that are utilized for very low-density lipoprotein assembly. However, due to the lack of useful antibodies to detect endogenous DGAT2 protein, it has been difficult to determine how this enzyme functions at the cellular level. We have unsuccessfully tested many commercial antibodies as well as our own “in-house” antibodies. There is currently no evidence that DGAT2 undergoes processing such that antigenic epitopes to these antibodies are removed. As an alternative, many studies have utilized epitope tagged versions of DGAT2 overexpressed in cells. These approaches can provide valuable information about a protein, but can be subject to artifacts, such as mislocalization, misregulation, protein aggregation and abnormal protein-protein interactions. In this study, we used gene editing with CRISPR/Cas9 to add three consecutive FLAG epitopes to the C-terminus of endogenous DGAT2 in HepG2 cells. HepG2 cells, derived from a human hepatocellular carcinoma, have been routinely used as a cell model to study human hepatocyte lipid and lipoprotein metabolism. Using this system allowed us to successfully detect DGAT2 expressed from its endogenous locus in HepG2 cells by immunoblotting with anti-FLAG antibodies.

257-OR: Short-Term Hyperglucagonemia Induces Adipose Tissue Insulin Resistance and Inflammation In Vivo

Although the effect of glucagon on glucose metabolism has been well characterized, its effect on adipose tissue and lipid metabolism in humans in vivo has been poorly studied with controversial results. We examined the effect of short-term hyperglucagonemia on adipocyte metabolism in 8 healthy normal glucose tolerant subjects (5M/3F, age=35±5, BMI = 24±1) who received a 12-hour (6PM to 6AM) glucagon infusion (6ng/kg/min) with 14C-glycerol infusion; subcutaneous abdominal adipose tissue biopsy was obtained at 6AM. 8 weeks later subjects returned for a repeat study with 12-hour infusion of normal saline. Plasma glucagon increased from 57±3 to 219±21 pg/ml within one hour and remained elevated throughout the study. Glycerol turnover rate (5.1±0.6 vs. 3.8±0.6 µmol/kg•min, p&amp;lt;0.05) increased by 34%, and the adipose tissue insulin resistance index (fasting plasma FFA x Insulin) more than doubled (5.8±0.8 vs. 2.8±0.7 mM•mU/L, p&amp;lt;0.05) after 12-hour glucagon infusion compared to saline. mRNA expression of genes involved in lipolysis in adipose tissue were upregulated after glucagon infusion (ATGL, 1.14±0.07 vs. 0.77±0.03; HSL, 1.17±0.03 vs. 0.9±0.13; MGL, 1.2±0.04 vs. 0.82±0.2, all p&amp;lt;0.05). Plasma concentration of proinflammatory markers (IL-1β, 0.65±0.05 vs. 0.49±0.05 pg/mL; TNF-α, 2.03±0.23 vs. 1.75±0.17 pg/mL, both p&amp;lt;0.05) and lipidomes involved in inflammatory pathways (lysophosphatidylcholine, 126±11 vs. 51±7 nmol/ml, p&amp;lt;0.005; phosphatidylcholine, 385±24 vs. 306±25 nmol/ml, p&amp;lt;0.01; ceramide, 1.7±0.2 vs. 1.2±0.2 nmol/ml, p&amp;lt;0.01) also increased after 12-hour glucagon infusion. H&amp;E and CD68 immunofluorescence staining in adipose tissue displayed the crown-like structures (CLS) and increased infiltration of macrophages following glucagon infusion. Conclusion: Short-term (12-hour) physiologic hyperglucagonemia stimulates adipose tissue lipolysis, induces adipocyte insulin resistance, and promotes adipose tissue and systemic inflammation. Disclosure X. Chen: None. M. Fourcaudot: None. L. Norton: None. R. A. Defronzo: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. D. Tripathy: None. Funding Foundation for Advancing Veterans’ Health Research

Lipid metabolism has been good to me

My career in research has flourished through hard work, supportive mentors, and outstanding mentees and collaborators. The Carman laboratory has contributed to the understanding of lipid metabolism through the isolation and characterization of key lipid biosynthetic enzymes as well as through the identification of the enzyme-encoding genes. Our findings from yeast have proven to be invaluable to understand regulatory mechanisms of human lipid metabolism. Several rewarding aspects of my career have been my service to the Journal of Biological Chemistry as an editorial board member and Associate Editor, the National Institutes of Health as a member of study sections, and national and international scientific meetings as an organizer. I advise early career scientists to not assume anything, acknowledge others’ accomplishments, and pay it forward.

Lead intoxication and beneficial effect of administering the aqueous extract of Artemisia absinthium on lipid metabolism and hypertension in male Wistar rats

Lead is a persistent and common environmental contaminant that can be found in food and water. It is well-known that lead acetate causes hyperten-sion, disturbance of lipid metabolism in humans and animals. Nowadays, the phytotherapy remains a very interesting field to recovery of deleterious effect of heavy metals. The aim of this study was to evaluate the effects of aqueous extract of Artemisia absinthium to modulating the effect of lead acetate induced changes in systolic and diastolic blood pressure levels, lipid profiles in serum, heart, aorta and liver tissues and determination of lead burden in blood, when added to intoxicated animal. Male rats (80-120) g were divided into four groups of six animals each. Intoxicated animals re-ceived intraperitoneally (i.p) injections of lead acetate (20 mg/kg/body weight) solution for 4 weeks every two days. Rats treated with plant receive orally the extract of A.absinthium (5%) for 4 weeks. Orally administration of the wormwood extract in rats intoxicated with lead acetate decreased sig-nificantly the systolic (SBP), diastolic blood pressure (DBP) and blood lead level. Levels of total lipids, TC and TG were decreased significantly in group (Pb+PL) compared to control, especially in heart and liver tissues. In serum, a significant elevation of TC and TG was noted in intoxicated rats compared to control. The cardiac damage induced by Pb was evidenced by an increase in the levels of LDH and AST. In conclusion, the data indicate that the worm-wood extract has a significant ability to reduce hypertension, blood lead lev-el, equilibrate lipid metabolism and cardiac enzymes level.