Lipidomic Analysis of Biological Samples by Liquid Chromatography Coupled to Mass Spectrometry

Astarita, Giuseppe; Ahmed, Faizy; Piomelli, Daniele

doi:10.1007/978-1-60761-322-0_10

Cited by 33 publications

(30 citation statements)

References 38 publications

(2 reference statements)

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“…Frozen punches were weighed and homogenized in methanol containing the following internal standards: d 8 -arachidonic acid, d 8 -2-arachidonoyl glycerol (Cayman Chemical, Ann Arbor, MI), diheptadecanoin, trinonadecenoin (Nu-Chek Prep, Elysian, MN). Lipids were analyzed as previously described (Astarita et al, 2009). Briefly, lipids were extracted with chloroform (2 vol) and washed with water (1 vol).…”

Section: Methodsmentioning

confidence: 99%

Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

et al. 2011

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Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific LPL-deficient mice. Homozygous mutant (NEXLPL-/-) mice were hyperphagic and became obese by 16 weeks of age. These traits were accompanied by elevations in the hypothalamic orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the hypothalamus of 3-month-old NEXLPL-/- mice. Moreover, deficiencies in essential fatty acids in the hypothalamus were evident by 3 months, with major deficiencies of long-chain n-3 fatty acids by 12 months. These results indicate that TG-rich lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide lipid signals for the central regulation of body weight and energy balance.

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Section: Methodsmentioning

confidence: 99%

Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

et al. 2011

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“…Lipid extractions were conducted as described [36]. Briefly, frozen brain samples were rapidly weighed and homogenized in ice-cold methanol containing appropriate internal standards (listed below).…”

Section: Methodsmentioning

confidence: 99%

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

et al. 2011

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The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio (‘desaturation index’) – displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = −0.80; P = 0.0001) and the Boston Naming test (r = −0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD.

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“…lipid profile, carbon metabolism, amino acids and nucleotides). Although other analytical methods are available for targeted study, MS and NMR methods have been widely adopted in targeted metabolomics research, because they offer superior analytical specificity, reproducibility and accurate quantification (Astarita, Ahmed, & Piomelli, 2009; Dudley et al, 2010). …”

Section: Overview Of Omics Technologies and Association Studiesmentioning

confidence: 99%

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

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2016

Advances in Genetics

337

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Complex and dynamic networks of molecules are involved in human diseases. High-throughput technologies enable omics studies interrogating thousands to millions of makers with similar biochemical properties (e.g. transcriptomics for RNA transcripts). However, a single layer of ‘omics’ can only provide limited insights into the biological mechanisms of a disease. In the case of GWAS, although thousands of SNPs have been identified for complex diseases and traits, the functional implications and mechanisms of the associated loci are largely unknown. Additionally, the genomic variants alone are not able to explain the changing disease risk across the life span. DNA, RNA, protein, and metabolite often have complementary roles to jointly perform a certain biological function. Such complementary effects and synergistic interactions between omic layers in the life-course can only be captured by integrative study of multiple molecular layers. Building upon the success in single-omics discovery research, population studies started adopting the multi-omics approach to better understanding the molecular function and disease etiology. Multi-omics approaches integrate data obtained from different omic levels to understand their interrelation and combined influence on the disease processes. Here, we summarize major omics approaches available in population research, and review integrative approaches and methodologies interrogating multiple omic layers, which enhance the gene discovery and functional analysis of human diseases. We seek to provide analytical recommendations for different types of multi-omics data and study designs to guide the emerging multi-omic research, and to suggest improvement of the existing analytical methods.

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Lipidomic Analysis of Biological Samples by Liquid Chromatography Coupled to Mass Spectrometry

Cited by 33 publications

References 38 publications

Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

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