scholarly journals Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11630-11635 ◽  
Author(s):  
Yan Wang ◽  
Markey C. McNutt ◽  
Serena Banfi ◽  
Michael G. Levin ◽  
William L. Holland ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Fed State ◽  
Beneficial Effects ◽  
Brown Adipose

Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.

scholarly journals Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule

2019 ◽  
Vol 40 (4) ◽  
pp. 1092-1107 ◽  
Author(s):  
Julian M Yabut ◽  
Justin D Crane ◽  
Alexander E Green ◽  
Damien J Keating ◽  
Waliul I Khan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Energy Homeostasis ◽  
De Novo ◽  
Nutrient Absorption ◽  
The Body ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Multiple Organs ◽  
Brown Adipose

Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

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

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

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.

scholarly journals Anti-Obesity Effect of Galacto-Oligosaccharides in Obese Rats

2021 ◽  
Author(s):  
Shang Kong ◽  
Xingjun Huang ◽  
Hua Cao ◽  
Yan Bai ◽  
Qishi Che ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fat Body ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Lipoprotein Cholesterol ◽  
Fat Cells ◽  
Expression Levels ◽  
Brown Adipose ◽  
Obese Rats

Abstract Background: Galacto-oligosaccharides (GOS) is a commonly used as a prebiotic with a variety of metabolic benefits. Whether GOS plays a protective role in obesity is still unknown. Here we demonstrated that GOS possesses an anti-obesity activity by promoting adipose tissue browning and thermogenesis. Results: Our results showed that GOS effectively slow weight gain of diet-induced obese (DIO) rats without affecting energy intake. GOS significantly suppressed the hypertrophy and hyperplasia of white adipose tissue (WAT), as well as markedly lessened the ratio of fat pad to fat body. Consistently, GOS significantly improved serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels, which indicated an appropriate weight loss activity of GOS. Interestingly, GOS also significantly increased the expression levels of browning proteins (UCP1, PPARγ, PGC1α and PRMD16) both in the WAT and brown adipose tissue (BAT). We further found that GOS markedly increased the expression levels of LXRα, PPARα, LDLR and CYP7A1 proteins in the liver of obese rats. Conclusions: Taken together, we concluded that GOS inhibits obesity by accelerating the browning of white fat cells and the thermogenesis of brown fat cells, moreover GOS improves host lipid homeostasis by promoting cholesterol catabolism.

scholarly journals Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers

2019 ◽  
Vol 109 (2) ◽  
pp. 260-268 ◽  
Author(s):  
Fredrik Rosqvist ◽  
Catriona A McNeil ◽  
Camilla Pramfalk ◽  
Sion A Parry ◽  
Wee Suan Low ◽  
...  
Keyword(s):  
Fatty Acid ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
De Novo Lipogenesis ◽  
Deuterated Water ◽  
Lipid Fractions ◽  
Habitual Diet ◽  
Fa Markers

ABSTRACT Background Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL. Objectives We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet. Methods Fasting hepatic DNL was assessed using 2H2O (deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions were determined by gas chromatography. Results Neither the lipogenic index (16:0/18:2n–6) nor the SCD index (16:1n–7/16:0) in VLDL-TG was associated with isotopically assessed DNL (r = 0.13, P = 0.1 and r = −0.08, P = 0.35, respectively). The relative abundances (mol%) of 14:0, 16:0, and 18:0 in VLDL-TG were weakly (r ≤ 0.35) associated with DNL, whereas the abundances of 16:1n–7, 18:1n–7, and 18:1n–9 were not associated. When the cohort was split by median DNL, only the abundances of 14:0 and 18:0 in VLDL-TG could discriminate between subjects having high (11.5%) and low (3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids, and red blood cell phospholipids were generally not associated with DNL. Conclusions The usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to discriminate clearly between individuals with low and high fasting hepatic DNL.

scholarly journals Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue

2020 ◽  
Vol 9 (1) ◽  
pp. 213
Author(s):  
Bárbara María Varela-Rodríguez ◽  
Paula Juiz-Valiña ◽  
Luis Varela ◽  
Elena Outeiriño-Blanco ◽  
Susana Belén Bravo ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Positive Impact ◽  
De Novo Lipogenesis ◽  
Beneficial Effects ◽  
Proteomic Approach ◽  
Subcutaneous Adipose

Bariatric surgery (BS) is the most effective treatment for obesity and has a positive impact on cardiometabolic risk and in the remission of type 2 diabetes. Following BS, the majority of fat mass is lost from the subcutaneous adipose tissue depot (SAT). However, the changes in this depot and functions and as well as its relative contribution to the beneficial effects of this surgery are still controversial. With the aim of studying altered proteins and molecular pathways in abdominal SAT (aSAT) after body weight normalization induced by BS, we carried out a proteomic approach sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis. These results were complemented by Western blot, electron microscopy and RT-qPCR. With all of the working tools mentioned, we confirmed that after BS, up-regulated proteins were associated with metabolism, the citric acid cycle and respiratory electron transport, triglyceride catabolism and metabolism, formation of ATP, pyruvate metabolism, glycolysis/gluconeogenesis and thermogenesis among others. In contrast, proteins with decreased values are part of the biological pathways related to the immune system. We also confirmed that obesity caused a significant decrease in mitochondrial density and coverage, which was corrected by BS. Together, these findings reveal specific molecular mechanisms, genes and proteins that improve adipose tissue function after BS characterized by lower inflammation, increased glucose uptake, higher insulin sensitivity, higher de novo lipogenesis, increased mitochondrial function and decreased adipocyte size.

scholarly journals Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

2010 ◽  
Vol 299 (3) ◽  
pp. R728-R739 ◽  
Author(s):  
Barbara E. Hasek ◽  
Laura K. Stewart ◽  
Tara M. Henagan ◽  
Anik Boudreau ◽  
Natalie R. Lenard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Uncoupling Protein ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Endocrine Function ◽  
Fischer 344 ◽  
Methionine Restriction ◽  
Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

scholarly journals ANGPTL3 Levels in Healthy and Mild Preeclamptic Pregnant Women

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A747-A747
Author(s):  
Maria F Garces ◽  
Roberto Franco - Vega ◽  
Luis M Maldonado - Acosta ◽  
Andres Castro - Pinzón ◽  
Javier Eslava-Schmalbach ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Study Groups ◽  
Normal Pregnancy ◽  
Lipoprotein Cholesterol ◽  
Fed State ◽  
The Third ◽  
Cholesterol Levels

Abstract Introduction: Throughout normal pregnancy, different metabolic and hormonal adaptations are presented, among others, significant modifications in the profile of lipids and lipoprotein metabolism. On the other hands, Angiopoietin-like protein 3 (ANGPTL3) are involved in the regulation of triglyceride metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. Objective: Thus, the objective of this study was to determine the profile of serum ANGPTL3 levels during three periods of gestation and three months after delivery. Design, setting and Participants: Serum ANGPTL3 levels were analyzed by ELISA, throughout pregnancy in a case-control study nested within a longitudinal prospective cohort of healthy pregnant (n = 52) and mild preeclamptic women (n = 20), women in the third month postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal, and anthropometric variables. Results: A significant reduction in ANGPTL3 levels was observed from the first to the third trimesters of pregnancy in healthy and preeclamptic pregnant women when compared with healthy non-pregnant and postpartum women (p<0.01). There were no significant differences in serum ANGPTL3 levels between normal and preeclamptic women. Serum ANGPTL3 levels were positively correlated with triglyceride, very-low-density lipoprotein cholesterol, and total cholesterol levels in healthy non-pregnant (p<0.05); whereas there were no significant correlations between ANGPTL3 with the same variables in healthy and preeclamptic pregnant women. Besides, there were no significant correlations between serum ANGPTL3 with body mass index, high-density lipoprotein cholesterol, glucose, insulin, leptin or HOMA-IR in the study groups described above. Conclusions: The results of the present study show for the first time that ANGPTL3 could be playing a fundamental role in the homeostasis of lipid metabolism throughout gestation. Thus, low levels of ANGPTL3 during pregnancy might favor the accumulation of lipid in oxidative tissues as a deposit of maternal energy source, while preserving glucose and amino acids for the fetus.

scholarly journals Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents

2021 ◽  
Author(s):  
Nela Maksimovic ◽  
Vanja Vidovic ◽  
Tatjana Damnjanovic ◽  
Biljana Jekic ◽  
Nada Majkic Singh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Fasting Glucose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Levels ◽  
Brown Adipose

IntroductionPositive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and LDL (low-density lipoprotein) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents.Material and methodsOur study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded.ResultsWe did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes.ConclusionsOur study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.

scholarly journals The Effect of Fructose Feeding on Intestinal Triacylglycerol Production and De Novo Fatty Acid Synthesis in Humans

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1781
Author(s):  
Simon Steenson ◽  
Fariba Shojaee-Moradie ◽  
Martin B. Whyte ◽  
Kim G. Jackson ◽  
Julie A. Lovegrove ◽  
...  
Keyword(s):  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Acute Effect ◽  
De Novo Lipogenesis ◽  
Fructose Intake ◽  
High Fructose ◽  
Catabolic Rate

A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (<2% energy) for 11 h. Oral 2H2O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of [2H5]-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG (p < 0.005) and VLDL-TAG (p = 0.003) were greater, and CM-TAG production rate (PR, p = 0.046) and CM-TAG fractional catabolic rate (FCR, p = 0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (p = 0.005) and apoB48 (p = 0.039), apoB100 (p = 0.013) and non-esterified fatty acids (NEFA) (p = 0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose (p = 0.043) and low-fructose (p = 0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase.

scholarly journals Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis

2019 ◽  
Vol 116 (22) ◽  
pp. 10937-10942 ◽  
Author(s):  
Wenhai Sui ◽  
Hongshi Li ◽  
Yunlong Yang ◽  
Xu Jing ◽  
Fei Xue ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Atherosclerotic Plaque ◽  
Ldl Cholesterol ◽  
Uncoupling Protein ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cerebrovascular Diseases ◽  
Plaque Development ◽  
Brown Adipose

Mirabegron (Myrbetriq) is a β3-adrenoreceptor agonist approved for treating overactive bladder syndrome in human patients. This drug can activate brown adipose tissue (BAT) in adult humans and rodents through the β3-adrenoreceptor-mediated sympathetic activation. However, the effect of the mirabegron, approved by the US Food and Drug Administration, on atherosclerosis-related cardiovascular disease is unknown. Here, we show that the clinical dose of mirabegron-induced BAT activation and browning of white adipose tissue (WAT) exacerbate atherosclerotic plaque development. In apolipoprotein E−/− (ApoE−/−) and low-density lipoprotein (LDL) receptor−/− (Ldlr−/−) mice, oral administration of clinically relevant doses of mirabegron markedly accelerates atherosclerotic plaque growth and instability by a mechanism of increasing plasma levels of both LDL-cholesterol and very LDL-cholesterol remnants. Stimulation of atherosclerotic plaque development by mirabegron is dependent on thermogenesis-triggered lipolysis. Genetic deletion of the critical thermogenesis-dependent protein, uncoupling protein 1, completely abrogates the mirabegron-induced atherosclerosis. Together, our findings suggest that mirabegron may trigger cardiovascular and cerebrovascular diseases in patients who suffer from atherosclerosis.

Sign in / Sign up

Export Citation Format

Share Document