The Insulin-Sensitizer Pioglitazone Remodels Adipose Tissue Phospholipids in Humans

The insulin-sensitizer pioglitazone exerts its cardiometabolic benefits in type 2 diabetes (T2D) through a redistribution of body fat, from ectopic and visceral areas to subcutaneous adipose depots. Whereas excessive weight gain and lipid storage in obesity promotes insulin resistance and chronic inflammation, the expansion of subcutaneous adipose by pioglitazone is associated with a reversal of these immunometabolic deficits. The precise events driving this beneficial remodeling of adipose tissue with pioglitazone remain unclear, and whether insulin-sensitizers alter the lipidomic composition of human adipose has not previously been investigated. Using shotgun lipidomics, we explored the molecular lipid responses in subcutaneous adipose tissue following 6months of pioglitazone treatment (45mg/day) in obese humans with T2D. Despite an expected increase in body weight following pioglitazone treatment, no robust effects were observed on the composition of storage lipids (i.e., triglycerides) or the content of lipotoxic lipid species (e.g., ceramides and diacylglycerides) in adipose tissue. Instead, pioglitazone caused a selective remodeling of the glycerophospholipid pool, characterized by a decrease in lipids enriched for arachidonic acid, such as plasmanylethanolamines and phosphatidylinositols. This contributed to a greater overall saturation and shortened chain length of fatty acyl groups within cell membrane lipids, changes that are consistent with the purported induction of adipogenesis by pioglitazone. The mechanism through which pioglitazone lowered adipose tissue arachidonic acid, a major modulator of inflammatory pathways, did not involve alterations in phospholipase gene expression but was associated with a reduction in its precursor linoleic acid, an effect that was also observed in skeletal muscle samples from the same subjects. These findings offer important insights into the biological mechanisms through which pioglitazone protects the immunometabolic health of adipocytes in the face of increased lipid storage.

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Fatty Acyl Esterification and Deesterification of 17β-Estradiol in Human Breast Subcutaneous Adipose Tissue

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-1762 ◽

2012 ◽

Vol 97 (9) ◽

pp. 3349-3356 ◽

Cited By ~ 12

Author(s):

Feng Wang ◽

Veera Vihma ◽

Maija Badeau ◽

Hanna Savolainen-Peltonen ◽

Marjut Leidenius ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Fatty Acyl ◽

Human Breast ◽

17Β Estradiol ◽

Subcutaneous Adipose

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Dietary intake of linoleic, linolenic, oleic, and arachidonic acid PPAR-gamma gene expression in visceral and subcutaneous adipose tissue among healthy subjects

Endocrine Abstracts ◽

10.1530/endoabs.49.ep642 ◽

2017 ◽

Author(s):

Emad Yuzbashian ◽

Maryam Zarkesh ◽

Golaleh Asghari ◽

Azita Zadeh-Vakili ◽

Behnaz Mahmoodi ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Arachidonic Acid ◽

Dietary Intake ◽

Subcutaneous Adipose Tissue ◽

Healthy Subjects ◽

Ppar Gamma ◽

Subcutaneous Adipose

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Improved Insulin Sensitivity during Pioglitazone Treatment Is Associated with Changes in IGF-I and Cortisol Secretion in Type 2 Diabetes and Impaired Glucose Tolerance

ISRN Endocrinology ◽

10.1155/2013/148497 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Lisa Arnetz ◽

Neda Rajamand Ekberg ◽

Charlotte Höybye ◽

Kerstin Brismar ◽

Michael Alvarsson

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Acth Stimulation Test ◽

Acth Stimulation ◽

Igf I ◽

Before And After ◽

Subcutaneous Adipose ◽

Pioglitazone Treatment

Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30–45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects () and increased during treatment ( to SD; ); no change was seen in IGT ( SD before and during treatment). Fasting glycerol decreased in T2D (), indicating reduced lipolysis. Fasting cortisol decreased in T2D ( to nmol/L; ) but increased in IGT ( to nmol/L; ). Peak cortisol was lower in T2D during treatment ( to , versus to nmol/L in IGT; ). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. This may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT.

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Membrane lipid profile of in vitro-produced embryos is affected by vitrification but not by long-term dietary supplementation of polyunsaturated fatty acids for oocyte donor beef heifers

Reproduction Fertility and Development ◽

10.1071/rd15414 ◽

2017 ◽

Vol 29 (6) ◽

pp. 1217 ◽

Cited By ~ 2

Author(s):

Beatriz C. S. Leão ◽

Nathália A. S. Rocha-Frigoni ◽

Ériklis Nogueira ◽

Elaine C. Cabral ◽

Christina R. Ferreira ◽

...

Keyword(s):

Mass Spectrometry ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Molecular Mechanisms ◽

Membrane Lipids ◽

Fatty Acyl ◽

Lipid Uptake ◽

Embryo Survival ◽

Lipid Species

Dietary rumen-protected polyunsaturated fatty acids (PUFAs) rich in linoleic acid (LA) may affect embryo yield, and LA can modulate the molecular mechanisms of lipid uptake in bovine blastocysts produced in vitro. In embryos, membrane lipids, such as phosphatidylcholines (PCs) and sphingomyelins (SMs), affect cryopreservation success. The aim of the present study was to evaluate embryonic developmental rates after the IVF of oocytes retrieved from Nellore heifers fed for approximately 90 days with rumen-protected PUFAs rich in LA. In addition, we evaluated embryo cryotolerance and the membrane structure lipid composition using matrix-assisted laser desorption ionisation mass spectrometry of fresh and vitrified embryos. Embryo development to the blastocyst stage (mean 43.2%) and embryo survival after vitrification and warming (mean 79.3%) were unaffected by diet. The relative abundance of one lipid species (PC ether (PCe; 38:2, which means that this lipid has 38 carbon atoms and 2 double bonds in the fatty acyl residues) was increased after PUFAs supplementation. However, 10 ions were affected by cryopreservation; ions consistent with PC 32:0, PC 34:1, SM 24:1, PC 40:6 or PC 42:9, PC plasmalogen (PCp) 44:10 or PC 42:7, triacylglycerol (TAG) 54:9 and a not assigned ion (m/z 833.2) were lower in blastocysts that survived to the cryopreservation process compared with fresh blastocysts, whereas the abundance of the ions PC 36:3 or PC 34:0, PCe 38:2 or PC 36:6 and PC 36:5 or PCe 38:1 were increased after cryopreservation. Thus, the results demonstrate that the mass spectrometry profiles of PC, SM and TAG species differ significantly in bovine blastocysts upon cryopreservation. Because the lipid ion abundances of fresh and vitrified–warmed embryos were distinct, they can be used as potential markers of post-cryopreservation embryonic survival.

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55 Sow Milk Lipidome Study Reveals Changes in Fatty Acyl Residues in Triglycerides and Phosphatidylglycerol, but Not in Plasma Membrane Phospholipids Across Lactation

Journal of Animal Science ◽

10.1093/jas/skab054.261 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 152-153

Author(s):

Sarah Luecke ◽

Aridany Suarez-Trujillo ◽

Lea Logan ◽

Kara R Stewart ◽

Christina Ferreira ◽

...

Keyword(s):

Plasma Membrane ◽

Milk Fat ◽

Membrane Lipids ◽

Multiple Reaction Monitoring ◽

Late Pregnancy ◽

Fatty Acyl ◽

Variable Component ◽

Membrane Phospholipids ◽

Mature Milk ◽

Lipid Species

Abstract Sow milk fat content is crucial to neonatal survival, as it is utilized for thermogenesis and nutrition. However, fat is the most variable component of milk in concentration and lipid species. Characterizing lipid changes across the course of a sow’s lactation may help identify molecules or systems to target to help enhance milk fat quality and quantity for neonatal survival and growth. Percent fat variation is greatest in colostrum, the first milk. Little is known regarding colostrum synthesis, other than it accumulates in the gland beginning in mid-late pregnancy, which is prior to the initiation of fatty acid synthesis in lactocytes. The objective of this study was to characterize changes in lipid composition of milk across the course of lactation and determine if there was a relationship between fat percent and lipid species in colostrum and mature milk. Milk was collected from 9 multiparous sows on days 0, 3, 7, and 14 relative to birth. Percent fat was determined by creamatocrit, and found to be different (p< 0.05) between day 0 (12.36 ± 5.90%) and day 3 (16.22 ± 3.65%) but not between day 7 (13.13 ± 2.19%) and 14 (12.13 ± 2.45%). Fat was extracted from milk using the Bligh-Dyer method and profiled using multiple reaction monitoring. Amounts of lipid species were calculated relative to standards and data analysis was performed using Metaboanalyst 4.0. Principle component analysis revealed lactation day had a significant effect on distribution of fats. Triacylglycerides (TAG), phosphatidylglycerol (PG), and plasma membrane lipids were modified from colostrum to mature milk, with a significant increase in PGs and TAGs across the course of lactation. Correlation analysis of percent fat with lipid concentration indicated strong relationships (P < 0.05; |r| >0.80) with eight lipids. No differences are found in the abundance of plasma membrane phospholipids, sphingomyelin, or cholesterol esters across lactation days.

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Microstructural morphology of sphingolipid dispersions as investigated by freeze-fracture EM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141093 ◽

1995 ◽

Vol 53 ◽

pp. 944-945

Author(s):

Vitthal S. Kulkarni ◽

Wayne H. Anderson ◽

Rhoderick E. Brown

Keyword(s):

Acyl Chain ◽

Biological Significance ◽

Freeze Fracture ◽

Fatty Acyl ◽

Fatty Acyl Moiety ◽

Aqueous Dispersions ◽

Head Groups ◽

Lipid Species ◽

Microstructural Morphology ◽

Layer Chromatography

The biological significance of the sphingomyelins (SM) and monoglycosylated sphingolipids like galactosylceramides (GalCer) are well documented Our recent investigation showed tubular bilayers in the aqueous dispersions of N-nervonoyl GalCer [N-(24:lΔ15,cls) GalCer] (a major fatty acyl moiety of natural GalCer). To determine the influence of lipid head groups on the resulting mesophasic morphology, we investigated microstructural self-assemblies of N-nervonoyl-SM [N-(24:1 Δ15,cls) SM; the second most abundant sphingomyelin in mammalian cell membranes], 1- palmitoyl-2-nervonoyl phosphatidylcholine [PNPC] (the lipid species with the same acyl chain configuration as in N-(24: 1) GalCer) and also compared it with egg-SM by freeze-fracture EM.Procedures for synthesizing and purifying N-(24:1) GalCer, N-(24:1) SM, and PNPC have been reported . Egg-SM was purchased from Avanti Polar Lipids, Alabaster AL. All lipids were >99% pure as checked by thin layer chromatography. Lipid dispersions were prepared by hydrating dry lipid with phosphate buffer (pH 6.6) at 80-90°C (3-5 min), vigorously vortexing (1 min) and repeating this procedure for three times prior to three freeze-thaw cycles.

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