Enhanced oleate uptake and lipotoxicity associated with laurate

Kitaura, Yasuyuki; Inoue, Kana; Kato, Naoya; Matsushita, Nahomi; Shimomura, Yoshiharu

doi:10.1016/j.fob.2015.05.008

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…Another mitigating factor towards the advent of steatohepatitis is the fact that a great proportion of fatty acids identified in the hApoD fatty liver were ω-6 and ω-3 PUFA. Lipotoxicity is typically associated with accumulation of saturated fatty acids such as palmitate [40] and monounsaturated fatty acids like oleate [41]. Relative to WT controls, transgenic fatty livers accumulate a smaller proportion of saturated and mono-unsaturated LCFA in favour of ω-6 and ω-3 fatty acids (Fig.5A&B).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis

Desmarais

Bergeron

Rassart

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. Overexpression of ApoD in mouse neural tissue induces the development of a noninflammatory hepatic steatosis in 12-month-old transgenic animals. Previous data indicates that accumulation of arachidonic acid, ApoD's preferential ligand, and overactivation of PPARγ are likely the driving forces in the development of the pathology. However, the lack of inflammation under those conditions is surprising. Hence, we further investigated the apparent repression of inflammation during hepatic steatosis development in aging transgenic animals. The earliest modulation of lipid metabolism and inflammation occurred at 6 months with a transient overexpression of L-PGDS and concomitant overproduction of 15d-PGJ 2 , a PPARγ agonist. Hepatic lipid accumulation was detectable as soon as 9 months. Inflammatory polarization balance varied in time, with a robust anti-inflammatory profile at 6 months coinciding with 15d-PGJ 2 overproduction. Omega-3 and omega-6 fatty acids were preferentially stored in the liver of 12-month-old transgenic mice and resulted in a higher omega-3/omega-6 ratio compared to wild type mice of the same age. Thus, inflammation seems to be controlled by several mechanisms in the liver of transgenic mice: first by an increase in 15d-PGJ 2 production and later by a beneficial omega-3/omega-6 ratio. PPARγ seems to play important roles in these processes. The accumulation of several omega fatty acids species in the transgenic mouse liver suggests that ApoD might bind to a broader range of fatty acids than previously thought.

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Section: Discussionmentioning

confidence: 99%

Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis

Desmarais

Bergeron

Rassart

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Although SFAs have been previously reported to induce mitochondrial dysfunction and apoptosis in several cell types (50,51,74), studies drawing associations between mitochondrial dysfunction and apoptotic effects of MCSFAs and LCSFAs in DRG neurons are limited. We found that palmitate and stearate induced significant increases in caspase 3/7 levels, whereas laurate and myristate had no effect on caspase 3/7 activation.…”

Section: Saturatedmentioning

confidence: 99%

Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons

Rumora

Lograsso

Haidar

et al. 2019

Journal of Lipid Research

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This article is available online at http://www.jlr.org experience a loss of sensation that occurs in a stockingand-glove distribution and has a severe impact on the individual's quality of life and societal productivity (3-7). The progressive loss of sensory function results from distal-toproximal peripheral nerve damage and dysfunction of sensory neurons. Although the pathogenesis of DPN is not fully understood, recent studies indicate that DPN pathogenesis is directly linked to a continuum of metabolic factors associated with dyslipidemia (8-10).Plasma concentrations of free saturated FAs (SFAs) are commonly elevated in T2D (11). In general, SFAs are classified as inducers of lipotoxicity (12, 13), mitochondrial dysfunction (14-17), and apoptosis (17); however, recent evidence indicates that hydrocarbon chain length of SFAs defines the level of intracellular lipotoxicity (18,19). Moreover, the Western diet, characterized by increased intake of foods with high levels of long-chain SFAs (LCSFAs), including myristate (C14:0), palmitate (C16:0), and stearate (C18:0), and low levels of beneficial medium-chain SFAs (MCSFAs), such as laurate (C12:0) (20-22), is a driving factor in the onset of dyslipidemia and T2D (23). MCSFAs are reported to prevent lipotoxicity and increase mitochondrial energy production (18,24,25). Likewise, equimolar caloric intake of MCSFAs and LCSFAs increases mitochondrial energy expenditure and leads to oxidative metabolic pathways as opposed to the metabolic dysfunction triggered by LCSFAs (24,26). SFAs are also directed to mitochondrial oxidative pathways through hydrocarbon chain length-dependent mechanisms; LCSFAs are targeted into the mitochondrial matrix for -oxidation through a transport system consisting of palmitoyltransferases (18,24,27), whereas MCSFAs are transported independently into the mitochondria, allowing for more efficient modulation of mitochondrial energy production (18,24). Hence, chain length of SFAs plays a critical role in regulating mitochondrial Abstract Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Because long-chain saturated FAs (SFAs) damage DRG neurons and medium-chain SFAs are reported to improve neuronal function, we evaluated . Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons. J. Lipid Res. 2019. 60: 58-70. Supplementary key words diabetes • dyslipidemias • apoptosis • palmitate • stearate • laurate • myristate • mitochondrial depolarizationDiabetic peripheral neuropathy (DPN) is a common complication that affects up to 30% of patients with prediabetes and 50% of T2D patients (1, 2). Patients with DPN

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“…Complete inhibition of growth was seen for C4, C8, and C10 fatty acids, suggesting that the lower range of fatty acid chain lengths impose fungicidal or fungistatic effects on this species. Fungal inhibition by free fatty acids is a well-documented, with reports of many plant- and animal-pathogenic fungi such as Botrytis cinerea, Fusarium oxysporum, and Candida albicans by fatty acids of different chain length and degree of saturation [ 64 , 65 , 66 , 67 ]. Antifungal free fatty acids are typically believed to act by becoming incorporated into the fungal cell membrane, thus increasing membrane fluidity and leading to destabilization and cell death; however, many other cellular pathways may be involved in these mechanisms and remain to be uncovered [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…As fatty acids with chain length smaller than lauric acid (< C12) were toxic, it is likely that lauric acid is at the edge of toxicity for R. laurciola . Lipid buildup within the cell membrane, as has been suggested previously as a primary mechanism for fatty acid cytotoxicity in fungi, could explain the bulging appearance of lauric acid-treated cells, as well as their diffuse lipid staining [ 65 , 66 ]. Alternatively, fatty acids may also accumulate in the endoplasmic reticulum, where fatty acids are converted into phosphatidic acid (PA) before conversion to diacylglycerols (DAGs) and triacylglycerols (TAGs) for LD formation, giving the appearance of diffuse staining within the cell.…”

Section: Discussionmentioning

confidence: 99%

Unique Attributes of the Laurel Wilt Fungal Pathogen, Raffaelea lauricola, as Revealed by Metabolic Profiling

et al. 2021

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Raffaelea lauricola is the causative agent of laurel wilt, a devastating disease of lauraceous trees. R. lauricola is also an obligate nutritional symbiont of several ambrosia beetle species who act as vectors for the pathogen. Here, we sought to establish the baseline “phenome” of R. lauricola with knowledge concerning its metabolic capability, expanding our understanding of how these processes are impacted by environmental and host nutrients. Phenotypic screening using a microarray of over one thousand compounds was used to generate a detailed profile of R. lauricola substrate utilization and chemical sensitivity. These data revealed (i) relatively restricted carbon utilization, (ii) broad sulfur and phosphate utilization, and (iii) pH and osmotic sensitivities that could be rescued by specific compounds. Additional growth profiling on fatty acids revealed toxicity on C10 substrates and lower, with robust growth on C12–C18 fatty acids. Conditions for lipid droplet (LD) visualization and LD dynamics were examined using a series of lipid dyes. These data provide unique insights regarding R. lauricola metabolism and physiology, and identify distinct patterns of substrate usage and sensitivity which likely reflect important aspects of the host-microbe interface and can be exploited for the development of strategies for mitigating the spread of laurel wilt.

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Enhanced oleate uptake and lipotoxicity associated with laurate

Abstract: HighlightsA combination of laurate and oleate synergistically enhances lipotoxicity.Cell death pathways influenced by a combination of oleate and laurate vary among cell types.Laurate increases oleate uptake.

Cited by 8 publications

References 39 publications

Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis

Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis

Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons

Unique Attributes of the Laurel Wilt Fungal Pathogen, Raffaelea lauricola, as Revealed by Metabolic Profiling

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