Sequential Ordered Fatty Acid α Oxidation and Δ9 Desaturation Are Major Determinants of Lipid Storage and Utilization in Differentiating Adipocytes†

Abstract Dyslipidemia is a characteristic of maternal obesity and previous studies have demonstrated abnormalities in fatty acid oxidation and storage in term placentas. However, there is little information about the effect of pre-pregnancy obesity on placental lipid metabolism during early pregnancy. The objective of this study was to determine the relationship between lipid profiles and markers of metabolism in placentas from obese and lean dams at midgestation. Mice were fed a western diet (WD) or normal diet (ND) and lysophosphatidylcholines (LPCs) and/or phosphatidylcholines (PCs) were measured in dam circulation and placenta sections using liquid chromatography–tandem mass spectrometry and mass spectrometry imaging, respectively. In WD dam, circulating LPCs containing 16:1, 18:1, 20:0, and 20:3 fatty acids were increased and 18:2 and 20:4 were decreased. In WD placenta from both sexes, LPC 18:1 and PC 36:1 and 38:3 were increased. Furthermore, there were moderate to strong correlations between LPC 18:1, PC 36:1, and PC 38:3. Treatment-, spatial-, and sex-dependent differences in LPC 20:1 and 20:3 were also detected. To identify genes that may regulate diet-dependent differences in placenta lipid profiles, the expression of genes associated with lipid metabolism and nutrient transport was measured in whole placenta and isolated labyrinth using droplet digital PCR and Nanostring nCounter assays. Several apolipoproteins were increased in WD placentas. However, no differences in nutrient transport or fatty acid metabolism were detected. Together, these data indicate that lipid storage is increased in midgestation WD placentas, which may lead to lipotoxicity, altered lipid metabolism and transport to the fetus later in gestation.

Download Full-text

Ovarian Cycle-Specific Regulation of Adipose Tissue Lipid Storage by Testosterone in Female Nonhuman Primates

Endocrinology ◽

10.1210/en.2013-1428 ◽

2013 ◽

Vol 154 (11) ◽

pp. 4126-4135 ◽

Cited By ~ 24

Author(s):

Oleg Varlamov ◽

Michael P. Chu ◽

Whitney K. McGee ◽

Judy L. Cameron ◽

Robert W. O'Rourke ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Sex Hormones ◽

Luteal Phase ◽

Fatty Acid Uptake ◽

Ovarian Cycle ◽

Lipid Storage ◽

Hormone Sensitive Lipase ◽

Acid Uptake ◽

Hormone Sensitive

Previous studies in rodents and humans suggest that hyperandrogenemia causes white adipose tissue (WAT) dysfunction in females, although the underlying mechanisms are poorly understood. In light of the differences in the length of the ovarian cycle between humans and rodents, we used a nonhuman primate model to elucidate the effects of chronic hyperandrogenemia on WAT function in vivo. Female rhesus macaques implanted with testosterone capsules developed insulin resistance and altered leptin secretion on a high-fat, Western-style diet. In control visceral WAT, lipolysis and hormone-sensitive lipase expression were upregulated during the luteal phase compared with the early follicular (menses) phase of the ovarian cycle. Hyperandrogenemia attenuated elevated lipolysis and hormone-sensitive lipase activity in visceral WAT during the luteal phase but not during menses. Under control conditions, insulin-stimulated Akt and Erk activation and fatty acid uptake in WAT were not significantly affected by the ovarian cycle. In contrast, testosterone treatment preferentially increased fatty acid uptake and insulin signaling at menses. The fatty acid synthase and glucose transporter-4 genes were upregulated by testosterone during the luteal phase. In summary, this study reveals ovarian stage-specific fluctuations in adipocyte lipolysis and suggests that male sex hormones increase and female sex hormones decrease lipid storage in female WAT.

Download Full-text

Hormone Signaling Linked to Silkmoth Sex Pheromone Biosynthesis Involves Ca2+/Calmodulin-dependent Protein Kinase II-mediated Phosphorylation of the Insect PAT Family Protein Bombyx mori Lipid Storage Droplet Protein-1 (BmLsd1)

Journal of Biological Chemistry ◽

10.1074/jbc.m111.250555 ◽

2011 ◽

Vol 286 (27) ◽

pp. 24101-24112 ◽

Cited By ~ 30

Author(s):

Atsushi Ohnishi ◽

J. Joe Hull ◽

Misato Kaji ◽

Kana Hashimoto ◽

Jae Min Lee ◽

...

Keyword(s):

Fatty Acid ◽

Protein Kinase ◽

Sex Pheromone ◽

Bombyx Mori ◽

Lipid Storage ◽

Pheromone Biosynthesis ◽

Dependent Protein Kinase ◽

Family Protein ◽

Protein Kinase Ii ◽

Dependent Protein

Species-specific sex pheromones released by female moths to attract conspecific male moths are synthesized de novo in the pheromone gland (PG) via the fatty acid biosynthetic pathway. This pathway is regulated by a neurohormone termed pheromone biosynthesis activating neuropeptide (PBAN), a 33-amino acid peptide that originates in the subesophageal ganglion. In the silkmoth, Bombyx mori, cytoplasmic lipid droplets, which store the sex pheromone (bombykol) precursor fatty acid, accumulate in PG cells. PBAN stimulates lipolysis of the stored lipid droplet triacylglycerols (TAGs) and releases the precursor for final modification. PBAN exerts its physiological function via the PG cell-surface PBAN receptor, a G protein-coupled receptor that belongs to the neuromedin U receptor family. The PBAN receptor-mediated signal is transmitted via a canonical store-operated channel activation pathway utilizing Gq-mediated phospholipase C activation (Hull, J. J., Kajigaya, R., Imai, K., and Matsumoto, S. (2007) Biosci. Biotechnol. Biochem. 71, 1993–2001; Hull, J. J., Lee, J. M., Kajigaya, R., and Matsumoto, S. (2009) J. Biol. Chem. 284, 31200–31213; Hull, J. J., Lee, J. M., and Matsumoto, S. (2010) Insect Mol. Biol. 19, 553–566). Little, however, is known about the molecular components regulating TAG lipolysis in PG cells. In the current study we found that PBAN signaling involves phosphorylation of an insect PAT family protein named B. mori lipid storage droplet protein-1 (BmLsd1) and that BmLsd1 plays an essential role in the TAG lipolysis associated with bombykol production. Unlike mammalian PAT family perilipins, however, BmLsd1 activation is dependent on phosphorylation by B. mori Ca2+/calmodulin-dependent protein kinase II rather than protein kinase A.

Download Full-text

Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1212887109 ◽

2012 ◽

Vol 109 (37) ◽

pp. 14966-14971 ◽

Cited By ~ 24

Author(s):

W. H. Brown ◽

M. P. Gillum ◽

H.-Y. Lee ◽

J. P. G. Camporez ◽

X.-m. Zhang ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Lipid Storage ◽

Amide Hydrolase ◽

Ectopic Lipid Storage ◽

Fatty Acid Amide

Download Full-text

Bovine Cumulus Cells Protect Maturing Oocytes from Increased Fatty Acid Levels by Massive Intracellular Lipid Storage

Biology of Reproduction ◽

10.1095/biolreprod.112.106062 ◽

2013 ◽

Vol 88 (6) ◽

pp. 164-164 ◽

Cited By ~ 58

Author(s):

H. Aardema ◽

F. Lolicato ◽

C. H. A. van de Lest ◽

J. F. Brouwers ◽

A. B. Vaandrager ◽

...

Keyword(s):

Fatty Acid ◽

Cumulus Cells ◽

Lipid Storage ◽

Intracellular Lipid

Download Full-text

Liver fatty acid-binding protein in two cases of human lipid storage

Molecular and Cellular Biochemistry ◽

10.1007/bf00231388 ◽

1990 ◽

Vol 98 (1-2) ◽

Cited By ~ 17

Author(s):

Lodovica Vergani ◽

Marina Fanin ◽

Andrea Martinuzzi ◽

Andrea Galassi ◽

Andrea Appi ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Lipid Storage ◽

Liver Fatty Acid ◽

Fatty Acid Binding ◽

Acid Binding Protein

Download Full-text

Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein–Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects

Biochemical Journal ◽

10.1042/bj2690107 ◽

1990 ◽

Vol 269 (1) ◽

pp. 107-113 ◽

Cited By ~ 11

Author(s):

J Radom ◽

R Salvayre ◽

T Levade ◽

L Douste-Blazy

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Chain Length ◽

Cell Lines ◽

Lymphoid Cell ◽

Lipid Storage ◽

Lymphoid Cells ◽

Lipid Storage Myopathy ◽

Fatty Acid Chain ◽

Lymphoid Cell Lines

The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After incubation for 1 h the distribution of fluorescent fatty acids taken up by the lymphoid cell lines also differed with the chain length, most of the fluorescence being associated with phospholipid and triacylglycerols. In contrast with P10 and P12, P4 was not incorporated into neutral lipids. When the cells were incubated for 24 h with the pyrene fatty acids, the amount of fluorescent lipids synthesized by the cells was proportional to the fatty acid concentration in the culture medium. After a 24 h incubation in the presence of P10 or P12, at any concentration, the fluorescent triacylglycerol content of MLSM cells was 2-5-fold higher than that of control cells. Concentrations of pyrene fatty acids higher than 40 microM seemed to be more toxic for mutant cells than for control cells. This cytotoxicity was dependent on the fluorescent-fatty-acid chain length (P12 greater than P10 greater than P4). Pulse-chase experiments permitted one to demonstrate the defect in the degradation of endogenously biosynthesized triacylglycerols in MLSM cells (residual activity was around 10-25% of controls on the basis of half-lives and initial rates of P10- or P12-labelled-triacylglycerol catabolism); MLSM lymphoid cells exhibited a mild phenotypic expression of the lipid storage (less severe than that observed in fibroblasts). P4 was not utilized in the synthesis of triacylglycerols, and thus did not accumulate in MLSM cells: this suggests that natural short-chain fatty acids might induce a lesser lipid storage in this disease.

Download Full-text