Free Glycerol Research Articles

Free glycerol correlate with post-heparin lipoprotein lipase activity and contribute to differentiate familial vs. multifactorial chylomicronemia

Free glycerol correlate with post-heparin lipoprotein lipase activity and contribute to differentiate familial vs. multifactorial chylomicronemia

439 Mechanism for loss of intradermal fat accompanying skin fibrosis

Fibrotic diseases contribute to approximately 45% of deaths in Europe and North America, and are characterized by an accumulation of extracellular matrix and loss of lipid-filled cells. Dermal fibrosis is a debilitating disease which serves as a model for studying universal trends in fibrosis such as lipid depletion. Intradermal adipocytes comprising the dermal white adipose tissue (DWAT) have diverse functions impacted by their lipid content. The mechanisms governing DWAT lipid depletion are not known nor are the effects of lipid depletion in causing fibrosis. Wnt signaling is dysregulated among fibrotic tissues and sustained Wnt signaling in mouse dermis is sufficient to cause dermal fibrosis including DWAT lipid depletion. Here we tested the following hypothesis: Wnt signaling and Wnt-responsive factors cause DWAT lipid depletion and subsequent dermal thickening. We developed a genetic mouse model of Wnt activation in the dermis resulting in inducible and reversible dermal thickening preceded by DWAT lipid depletion, enabling us to identify mediators of Wnt-induced lipid depletion. Wnt activation in intradermal adipocytes in vitro leads to lipid loss by induction of lipolysis, as indicated by a three-fold increase in free glycerol, suggesting Wnt signaling causes cell autonomous lipolytic effects. Additionally, conditioned media from Wnt-activated fibroblasts stimulate lipid loss in intradermal adipocytes in vitro, implicating intercellular communication in fibrotic adipocyte lipid loss. Finally, transient inhibition of a candidate Wnt-responsive factor, CD26/DPPIV, in genetic and chemical models of fibrosis leads to preservation or faster recovery of lipid in DWAT and reduced dermal thickness in vivo, demonstrating that Wnt-DPPIV modulates lipid homeostasis in adipocytes impacting neighboring dermal fibroblasts. Thus, we propose to treat dermal fibrosis in a pre-clinical model with FDA-approved drugs by targeting a new cellular player in fibrosis.

SUN-105 Females Have Reduced Meta-Inflammation in Two States of Increased Adiposity, Obesity, and Aging

Obesity is a global health epidemic, closely associated with cardiovascular diseases (CVD), hypertension, type 2 diabetes, and atherosclerosis. Obese adipose tissue is a site and source for inflammation that is strongly associated with these metabolic diseases. In obese mice models, males exhibit profound adipose tissue macrophage (ATM) accumulation in gonadal white adipose tissue (GWAT) linked to insulin resistance, while females are protected even with enhanced adiposity. This dampened inflammation may directly explain reduced metabolic and cardiovascular disease in young women. However, it is not clear what metabolic and inflammatory responses occur in post-menopausal models. We hypothesized an increased inflammatory response would occur in obese older females. We challenged male and female C57Bl6/j mice to 16-24 weeks of 60% high fat diet (HFD) starting at 6 weeks of age (young) or 10 month of age (old). Animal body weights and metabolic depot (adipose and liver) weights were measured at the completion of diet challenge. Flow cytometry was used to determine ATM populations in visceral (GWAT) compared to subcutaneous inguinal WAT (IWAT). Lipolysis was stimulated with a beta3 adrenergic receptor (ADRB3) agonist CL-316, 243 and free fatty acids (FFA), glycerol, and triglyceride (TG) levels assessed in serum and liver. Obesity in young mice led to fat accumulation in GWAT and IWAT of both males and females. In old male animals, fat pads did not expand, and liver weights were as a result larger than in females. Both young and old females had reduced adipose inflammation compared to males. ADRB3 activation had no effect on adipose tissue weights but significantly increased liver weights in obese young females. Obese CL treated young and old female mice showed elevated FFA compared to levels induced in males. Lipolysis promoted appearance of crown like structures (CLS) in both obese young and old males and females, due to CD11c- ATM accumulation. Obesity during aging continues to lead to enhanced inflammation in males along with steatosis but females continue to be protected with appropriate storage of fatty acids with very little induced inflammation. Sex differences in inflammation that persist in aging demonstrate that differences in meta-inflammation may explain sex differences in metabolic and cardiovascular diseases regardless of age and need to be further explored for targeted treatment strategies.

The Rat (Rattus norvegicus) as a Model Object for Acute Organophosphate Poisoning. 1. Biochemical Aspects

The long-term effects of acute organophosphate (OP) poisoning remain poorly studied, while experimental models usually disregard species-related specificity of rodents as model objects. Here we present two toxicological models and a comparative analysis of a wide range of biochemical blood indices in their dynamics over 3 months after acute rat poisoning with paraoxon. As expected, the most sensitive biochemical index within the first hours and days after OP poisoning was whole blood acetylcholinesterase activity, which decreased by almost an order of magnitude in all experimental groups 3 h after poisoning. Changes in the parameters of carbohydrate and fat metabolism (triglyceride, free fatty acid, D-3-hydroxybutyrate, cholesterol and glycerol levels) were detected in experimental groups at different time points after poisoning. Statistically significant changes in a number of biochemical markers were found in positive control rats relative to intact rodents.

Techno-Economic and Life Cycle Impacts Analysis of Direct Methanation of Glycerol to Bio-Synthetic Natural Gas at a Biodiesel Refinery

An economic and environmental feasibility study were carried out on the thermochemical conversion of glycerol to medium methane content biological synthetic natural gas (bio-SNG). A plant that processed 497 kg·h−1 of glycerol to bio-SNG was modelled as an on-site addition to a soybean biodiesel plant based in Missouri (USA) that produced 30 million litres of soybean biodiesel per year. Assuming the glycerol contained only 80 wt% free glycerol, the bio-SNG could substitute up to 24% of the natural gas at the soybean biodiesel plant. The discounted cash flow analysis showed it was possible to generate positive NPVs and achieve internal rates of return within the hurdle rate (12%) for biomass gasification technologies. From the environmental analysis it was found that the bio-SNG could reduce global warming potential by 28% when compared to conventional natural gas in the USA and translates to roughly 7% reduction in biodiesel natural gas emissions, if the maximum 24% of natural gas were to be substituted by bio-SNG. The work highlights the potential to divert waste glycerol to an onsite energy vector at soybean biodiesel plants with minimal change to the main biodiesel production process and potential reductions to soybean biodiesel global warming potential.

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity.

Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs.

Energetic investment associated with vitellogenesis induces an oxidative cost of reproduction

Oxidative stress is a potential cost of reproduction, but conclusive evidence for this relationship is lacking. The goal of this study was to serially assess across a seasonal gradient the relationship between reproduction, circulating plasma energy metabolites and oxidative state. Here, we examine a study animal ideally suited to test for the oxidative costs of reproduction: the Allen Cays Rock Iguana. Female rock iguanas reproduce at varying frequencies, often skipping years, allowing for a comparison between reproductive and non-reproductive females during the same narrow, annual breeding season. This feature of iguana life history enabled us to address not just sex and seasonal differences in physiology, but also potential oxidative costs of reproduction in females. Male and female iguanas were sampled during the early (vitellogenic), late (gravid) and post-reproductive seasons. Ultrasound examinations were performed on females to quantify reproductive investment, and blood samples were collected for physiology assays, which included reactive oxygen metabolites (d-ROMs), antioxidants, triglycerides, free glycerol and glucose. The early reproductive season was characterized by significant increases in reproductive female's triglycerides, free glycerol and oxidative stress compared to late and post-reproductive periods and non-reproductive females and males during all sampling periods. Antioxidants were significantly elevated during the early reproductive season for reproductive females, non-reproductive females and males when compared to late and post-season. Follicle number in early reproductive females was positively related to d-ROMs, triglycerides and free glycerol, negatively related to antioxidants and showed no relationship with glucose. Measures of oxidative stress, d-ROMs and oxidative index were positively correlated with circulating levels of the lipid metabolite free glycerol during the early reproductive period, but this relationship weakened in the late season and disappeared in the post-season. Broadly, this study supports the hypothesis that the relationship between reproduction and oxidative stress is driven by energy investment, being greatest during early reproduction when vitellogenesis is occurring.

The herbicide quinclorac as potent lipase inhibitor: Discovery via virtual screening and in vitro/in vivo validation.

Lipolysis is primarily controlled by the stepwise action of hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL) to release free fatty acids and glycerol. A high level of circulating free fatty acids is well-known to mediate insulin resistance. Thus, the need to discover lipase inhibitors against both enzyme systems remains urgent. Agrochemicals are tightly regulated chemicals and therefore are potential source of new medicinal agents. Accordingly, we implemented a computational workflow to search for new lipase inhibitory leads by virtually screening commercial agrochemicals against HSL and MGL employing binding pharmacophores and docking experiments. Ten agrochemicals were identified as potential lipase inhibitors, out of which quinclorac, a safe herbicide, achieved high-ranking score. Subsequent in vitro evaluation against rat epididymal lipase activity showed quinclorac to exhibit nanomolar anti-lipase IC50 . Subsequent in vivo testing showed quinclorac to significantly decrease blood glycerol levels after acute exposure (150mg/kg) and multiple dosing (50 or 25mg/kg) (p<0.05).

Investigation of different levels of glycerol on cyst hatching percentage, total length and survival of Phallocryptus spinosa and Artemia franciscana

Artemia and fairy shrimps due to propitious size and wide distribution throughout the world, purvey ample feed resources with relatively favorable nutritional value to profitable aquatic species. Ambient water physical-chemical properties affect the biological function of zooplanctonic cysts. Glycerol is an alcoholic compound which is soluble in water and it has three hydroxyl groups that are responsible for solubility in water. There is a relationship between the presence of free glycerol in water and cysts metabolic rate and dormancy duration. The present study aimed to investigate the effects of different levels of free glycerol in the hatchery water on hatching percentage, total length of nauplius and mortality rate of Phallocryptus spinosa and Artemia franciscana cysts. In this experiment, four triplicate treatments including 0% (control), 0.1%, 1% and 10% of glycerol were used on A. franciscana and P. spinosa hatchery water for 48 hours and 72 hours, respectively. The results revealed that 0.1% glycerol was the most efficient level for hatching percentage of P. spinosa cysts with 28.86±1.6%. Also, the size of total length of newly hatched nauplii in this treatment was 0.75±0.08 mm that was significantly greater than the other treatments ( P ≤0.05); there was no significant difference in the mortality percentage between this treatment and the control treatment. In A. franciscana, the highest hatching rate (68.33±4.71%) and nauplius length (0.90±0.08 mm) were recorded in the 1% glycerol treatment. According to the results, glycerol at 0.1% level for P. spinosa and 1% level for A. franciscana are suitable in the cysts hatching media to increase hatching rate and nauplii performance. Our work could contribute to a better understanding of the hatching biology of dormant life stages in zooplanctonic crustaceans.

Determinação de Glicerina Livre em Biodiesel Utilizando Espectroscopia UV Visível: Estudo de Validação do Método

High glycerol content in biodiesel impairs engine performance. Brazilian legislation, (ANP Resolution 42/2004), limits the maximum of 0.02% w/w for free glycerol in biodiesel. The ASTM D6584 standard method for glycerol determination is gas chromatography, a time consuming and expensive technique. As alternative, free glycerol in biodiesel can be determined, after derivatization, by absorption spectroscopy in the visible region (410 nm). In this work, we have used a validation protocol for the spectroscopy method. Results indicate that the proposed method is linear (r2 = 0.993) for the studied concentration range and has acceptable accuracy and precision. The method presented relative standard deviations values of intermediate repeatability and accuracy below 5.0%. To calculate the limits of detection and quantification, three different calculation methods were used. Two of them resulted in appropriate quantification limits for glycerol. However, for the INMETRO calculation method, we found a higher value of quantification limit. Considering that the method is based on a chemical derivatization reaction, to produce a color product, the robustness of the method was analyzed for small changes in reaction temperature, wavelength and type of cuvette used in measurements. The results have shown that the method is robust for small variations in the reaction temperature, but not for small changes in wavelength and type of cuvette used (glass or plastic cuvette).

Forskolin reduces fat accumulation in Nile tilapia (Oreochromis niloticus) through stimulating lipolysis and beta-oxidation

High fat diets are commonly used in aquaculture to reduce feed cost in Nile tilapia, but impair its lipid homeostasis. This study evaluated the role of forskolin on reducing fat accumulation in Nile tilapia (Oreochromis niloticus) by using in vitro and in vivo experiments. The use of 50 μM forskolin in vitro increased free fatty acid and glycerol release, but decreased triglyceride in adipocytes and hepatocytes. The adipose triglyceride lipase (ATGL), protein kinase cAMP-dependent type I regulatory subunit alpha (PKAR I) and other genes related to β-oxidation (peroxisome proliferator activated receptor alpha, PPARα and carnitine O-palmitoyltransferase 1, CPT1) were significantly up-regulated. After feeding a high-fat diet for six weeks, O. niloticus were fed with 0 (control), 0.5 and 1.5 mg/kg forskolin for two weeks to determine whether forskolin could reduce fat accumulation in vivo. Fish fed the two levels of forskolin decreased significantly the hepatosomatic and mesenteric fat indices. The total lipid in the whole fish and liver together with the serum glycerol content were lower in fish fed on forskolin than in the control. The fish fed on forskolin diets exhibited smaller areas of lipid droplets in adipose and liver tissues. Lipolysis related genes (ATGL, hormone-sensitive lipase, HSL; monoacylglycerol lipase, MGL; and protein kinase cAMP-activated catalytic subunit, PKAC) and β-oxidation genes (PPARα; fatty acid binding protein 1, FABP1; and CPT1) in the adipose were up-regulated. Similarly, in the liver lipolysis genes such as ATGL and PKAR I and β-oxidation genes (PPARα, FABP1, CPT1 and acyl-CoA oxidase, ACO) showed an increasing trend with the increase of forskolin doses. This study indicates that forskolin can reduce fat accumulation in the adipose and liver by stimulating lipolysis and β-oxidation in O. niloticus.

Induction of fat apoptosis by a non-thermal device: Mechanism of action of non-invasive high-intensity electromagnetic technology in a porcine model.

ObjectivesWhile controlled thermal changes in subcutaneous tissue have been used to trigger apoptosis of fat cells and have been proven clinically efficacious, another mechanism of electromagnetic stress suggests that fat apoptosis could be achieved by a non‐thermal manner as well. This animal model study investigates the use of a non‐invasive high‐intensity magnetic field device to induce apoptosis in fat cells.MethodsYorkshire pigs (N = 2) received one treatment (30 minutes) in the abdominal area using a High‐Intensity Focused Electromagnetic (HIFEM) device. Punch biopsy samples of fat tissue and blood samples were collected at the baseline, 1 and 8 hours after the treatment. Biopsy samples were sectioned and evaluated for the levels of an apoptotic index (AI) by the TUNEL method. Statistical significance was examined using the rANOVA and Tukey's test (α 5%). Biopsy samples were also assessed for molecular biomarkers. Blood samples were evaluated to determine changes related to fat and muscle metabolism. Free fatty acids (FFA), triacylglycerol (TG), glycerol and glucose (Glu) were used as the main biomarkers of fat metabolism. Creatinine, creatinine kinase (CK), lactate dehydrogenase (LDH) and interleukin 6 (IL6) served as the main biomarkers to evaluate muscle metabolism.ResultsIn treated pigs, a statistically significant increase in the apoptotic index (AI) (P = 1.17E‐4) was observed. A significant difference was found between AI at baseline (AI = 18.75%) and 8‐hours post‐treatment (AI = 35.95%). Serum levels of fat and muscle metabolism indicated trends (FFA −0.32 mmol · l−1, −28.1%; TG −0.24 mmol · l−1, −51.8%; Glycerol −5.68 mg · l−1, −54.8%; CK +67.58 μkat · l−1, +227.8%; LDH +4.9 μkat · l−1,+35.4%) suggesting that both adipose and muscle tissue were affected by HIFEM treatment. No adverse events were noted to skin and surrounding tissue.ConclusionsApplication of a high‐intensity electromagnetic field in a porcine model results in adipocyte apoptosis. The analysis of serum levels suggests that HIFEM treatment influences fat and muscle metabolism. Lasers Surg. Med. 51:47–53, 2019. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Free Glycerol Removal from Biodiesel Using Anion Exchange Resin as a New Type of Adsorbent

Anion exchange resins, as a new class of adsorbents for glycerol removal, were proposed and compared with cation exchange resins and macroporous resins. These kinds of resins exhibited excellent ad...

Elevation of blood lipids in hepatocyte-specific fatty acid transport 4-deficient mice fed with high glucose diets

Fatty acid transport protein4 (FATP4) is upregulated in acquired and central obesity and its polymorphisms are associated with blood lipids and insulin resistance. Patients with FATP4 mutations and mice with global FATP4 deletion exhibit skin abnormalities characterized as ischthyosis prematurity syndrome (IPS). Cumulating data have shown that an absence of FATP4 increases the levels of cellular triglycerides (TG). However, FATP4 role and consequent lipid and TG metabolism in the hepatocyte is still elusive. Here, hepatocyte-specific FATP4 deficient (Fatp4L−/−) mice were generated. When fed with chow, these mutant mice displayed no phenotypes regarding blood lipids. However when fed low-fat/high-sugar (HS) or high-fat/high-sugar (HFS) for 12 weeks, Fatp4L−/− mice showed a significant increase of plasma TG, free fatty acids and glycerol when compared with diet-fed control mice. Interestingly, Fatp4L−/− mice under HS diet had lower body and liver weights and they were not protected from HFS-induced body weight gain and hepatic steatosis. Male mutant mice were more sensitive to HFS diet than female mutant mice. Glucose intolerance was observed only in female Fatp4L−/− mice fed with HS diet. Lipidomics analyses revealed that hepatic phospholipids were not disturbed in mutant mice under both diets. Thus, hepatic FATP4 deletion rendered an increase of blood lipids including glycerol indicating a preferential fatty-acid channeling to TG pools that are specifically available for lipolysis. Our results imply a possible risk of hyperlipidemia as a result of abnormal metabolism in liver in IPS patients with FATP4 mutations who consume high-sugar diets.

Energy and metabolic pathways in trefoil factor family member 2 (Tff2) KO mice beyond the protection from high-fat diet-induced obesity

AimsTrefoil factor family member 2 (TFF2) is a small gut peptide. We have previously shown that Tff2 knock out (KO) mice are protected from high-fat (HF) diet-induced obesity (De Giorgio et al., 2013a). Thus, exploring Tff2 KO-related pathways of mice at the genomic, proteinic and biochemical levels would allow us to elucidate the processes behind this protection from obesity. Main methodsTo explore the metabolic and energetic effects related to Tff2 deficiency, we used sampled blood from the previous study to measure levels of free fatty acids, glucose, glycerol and triglycerides in serum. Expression levels of selected genes and proteins related to energy metabolism in the skeletal muscle, liver and adipose tissue were also studied. Key findingsFollowing the 12-wk challenging of Tff2 KO and WT mice with both HF and low-fat diet, Tff2 KO mice had lower levels of serum glucose, triglycerides and glycerol. Importantly, western blotting and Q_RT-PCR revealed that the expression levels of selected genes and proteins are toward less fat storage and increased energy expenditure by enhancing lipid and glucose utilization via oxidative phosphorylation. SignificanceWe mapped a part of the metabolic and biochemical pathways of lipids and glucose involving the adipose tissue, liver, skeletal muscle and sympathetic nervous system that protect Tff2 KO mice from the HF diet-induced obesity. Our data highlight Tff2-related pathways as potential targets for obesity therapies.

Modification of Chemical Properties of Shellac with Glycerol and Acrylic Acid

Shellac is a natural product which has been presumed as a fragile polymer due to itschemical properties. The objective of this study was to improve chemical properties of shellac by themodification with different concentration of glycerol and acrylic acid. Shellac was reacted withglycerol at various temperature and amounts of glycerol. The intermediate product was reacted withacrylic acid at different concentration. Acid value, hydroxyl groups, and free glycerol concentrationof modified shellac was determined. The result showed that acid value gradually decrease alongincreasing temperature for each ratio of glycerol and acrylic acid to shellac. The concentration ofhydroxyl groups rise as temperature and ratio increases. Furthermore, free glycerol concentration felldown along with the rise temperature. Modification chemical properties of shellac with glycerol andacrylic acid can be applied for the further study to enhance shellac properties.

Production of Cold-Active Lipase by Free and Immobilized Marine Bacillus cereus HSS: Application in Wastewater Treatment.

Lipases are enzymes that have the potential to hydrolyze triacylglycerol to free fatty acids and glycerol and have various applications. The aim of the present study was to isolate and screen marine bacteria for lipase production, optimize the production, and treat wastewater. A total of 20 marine bacterial isolates were obtained from the Mediterranean Sea and were screened for lipase production. All isolates were found to have lipolytic ability. The differences between the isolates were studied using RAPD-PCR. The most promising lipase producer (isolate 3) that exhibited the highest lipolytic hydrolysis (20 mm) was identified as Bacillus cereus HSS using 16S rDNA analysis and had the accession number MF581790. Optimization of lipase production was carried out using the Plackett–Burman experimental design with cotton seed oil as the inducer under shaking conditions at 10°C. The most significant factors that affected lipase production were FeSO4, KCl, and oil concentrations. By using the optimized culture conditions, the lipase activity increased by 1.8-fold compared with basal conditions. Immobilization by adsorption of cells on sponge and recycling raised lipase activity by 2.8-fold compared with free cells. The repeated reuse of the immobilized B. cereus HSS maintained reasonable lipase activity. A trial for the economic treatment of oily wastewater was carried out. Removal efficiencies of biological oxygen demand, total suspended solids, and oil and grease were 87.63, 90, and 94.7%, respectively, which is promising for future applications.

Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice.

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro.

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO's ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.

Lipid Droplets Breakdown: Adipose Triglyceride Lipase Leads the Way

Previously in Current Protein & Peptide Science, Cerk et al. (2018) reported an updated review of concepts and knowledge regarding structure, function and regulatory mechanism of the adi-pose triglyceride lipase (ATGL), one of the key-enzyme required for intracellular lipolysis. Until recently, lipid droplets (LDs) were just considered as neutral lipid storage sites, thus providing energy through lipolysis and β-oxidation pathway when required during stressful conditions [1]. Nowadays, it is clearly established that LDs are well-organized and extremely dynamic cellular organelles, conserved in eubacteria, fungi, plants and animals plants and animals where they are essential for lipid homeostasis and energy maintenance [2]. Alteration of these two critical physiological processes can lead to important metabolic disorders [3]. The conventional snapshot representation of LDs remains a suitable model for defining their general composition which is based on a central organic core of neutral lipids (mainly triacylglycerol (TAG) and sterol esters) surrounded by a phospholipid monolayer [4], associated with a wide range of structural [5], enzymatic [6] and membrane-trafficking proteins [7]. However, we also know that proteins and lipid species of such structures can be extremely diversified depending on the different cell types or metabolic status. Interestingly, LDs anabolism and catabo-lism are well-balanced, and tightly-controlled biological mechanisms involving a large number of actors at both tran-scriptional, translational and post-translational levels [8]. TAG-containing LDs breakdown is achieved during extended starvation period or enhanced energy demand, and this phenomenon is mainly mediated by three distinct lipolytic enzymes (i.e., the adipose triglyceride lipase (ATGL), the hormone-sensitive lipase (HSL) and the mono-glyceride lipase (MGL)) that act sequentially to finally generate free fatty acids (FFA) and glycerol molecules [8]. Since ATGL catalyzes the first step of this essential lipolytic pathway , it is thus crucial to fully define the physiological func-tion(s) and structural properties of this protein, but also to get insights onto the regulatory mechanisms governing ATGL action towards LDs [9].