Regulation of energy metabolism by long-chain fatty acids

Nakamura, Manabu; Yudell, Barbara E.; Loor, Juan J.

doi:10.1016/j.plipres.2013.12.001

Cited by 590 publications

(462 citation statements)

References 259 publications

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“…The function of the PDKs is to inhibit PDH by phosphorylation under conditions in which pyruvate oxidation is to be repressed, such as in starvation (19,20). An aberrant increase in PDK expression may therefore cause impaired PDH function in ME/ CFS, possibly via activity of PPAR transcription factors (23). PPARD mRNA was significantly upregulated in PBMCs of ME/CFS patients, while PPARA showed no difference compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…There was, however, a positive correlation between the expression of PDK1 and both of these PPARs. Even if expression of the PPAR target gene ACOX1 was similar in ME/CFS patients and controls, it cannot be excluded that the PPARs contribute in the regulation of PDKs at some stage of ME/CFS disease development (23). The mitochondrial enzyme SIRT4 was recently reported to inhibit PDH activity by hydrolyzing lipoamide cofactors from the E2 component of the PDH complex (21).…”

Section: Discussionmentioning

confidence: 99%

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Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

et al. 2016

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“…In mammals, excess energy is stored primarily as TAGs, which are mobilized when energy demands arise (Nakamura et al, 2014). FAs are the main components of adipose tissue (Drevon, 2005) that are stored as TAGs (Carracedo et al, 2013).…”

Section: Adipokinesmentioning

confidence: 99%

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Saavedra‐García

Nichols

Mahmud

et al. 2018

Molecular and Cellular Endocrinology

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Keywords:Fatty acids Cancer Lipid metabolism FOXO3 FOXM1 AKT/PI3K pathway a b s t r a c t Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance.Free fatty acids (FFAs), FA synthesis and b-oxidation are associated with cancer development and progression. Meanwhile, insulin and some adipokines, that are up-regulated by FAs, are also involved in cancer development and poor prognosis. In this review, we discuss the role of FA metabolism in cancer and how FA metabolism integrates with the FOXO3-FOXM1 axis. These new insights may provide leads to better cancer diagnostics as well as strategies for tackling cancer development, progression and drug resistance.

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“…Despite the surge of research for identifying cellular and molecular regulators of brown fat development (2,3), the role of dietary constituents, particularly dietary fatty acids (FA), in thermogenic activation is poorly understood. Depending on the degree of desaturation and the n-6/n-3 ratio, FA differentially control adiposity, insulin sensitivity, immune response (4), and probably energy expenditure (5)(6)(7). Lately, it has been suggested that n-3 polyunsaturated FA (PUFA) stimulate beige/brown adipogenesis in primary murine adipogenic precursor cells (5) as well as C57BL/6 mice (6, 7).…”

mentioning

confidence: 99%

Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-dependent Up-regulation of miR-30b and miR-378

Kim

Okla

Erickson

et al. 2016

Journal of Biological Chemistry

101

120

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Emerging evidence suggests that n-3 polyunsaturated fatty acids (PUFA) promote brown adipose tissue thermogenesis. However, the underlying mechanisms remain elusive. Here, we hypothesize that n-3 PUFA promotes brown adipogenesis by modulating miRNAs. To test this hypothesis, murine brown preadipocytes were induced to differentiate the fatty acids of palmitic, oleate, or eicosapentaenoic acid (EPA). The increases of brown-specific signature genes and oxygen consumption rate by EPA were concurrent with up-regulation of miR-30b and 378 but not by oleate or palmitic acid. Next, we hypothesize that free fatty acid receptor 4 (Ffar4), a functional receptor for n-3 PUFA, modulates miR-30b and 378. Treatment of Ffar4 agonist (GW9508) recapitulated the thermogenic activation of EPA by increasing oxygen consumption rate, brown-specific marker genes, and miR-30b and 378, which were abrogated in Ffar4-silenced cells. Intriguingly, addition of the miR-30b mimic was unable to restore EPA-induced Ucp1 expression in Ffar4-depleted cells, implicating that Ffar4 signaling activity is required for up-regulating the brown adipogenic program. Moreover, blockage of miR-30b or 378 by locked nucleic acid inhibitors significantly attenuated Ffar4 as well as brown-specific signature gene expression, suggesting the signaling interplay between Ffar4 and miR-30b/378. The association between miR-30b/378 and brown thermogenesis was also confirmed in fish oil-fed C57/BL6 mice. Interestingly, the Ffar4 agonism-mediated signaling axis of Ffar4-miR-30b/378-Ucp1 was linked with an elevation of cAMP in brown adipocytes, similar to cold-exposed or fish oil-fed brown fat. Taken together, our work identifies a novel function of Ffar4 in modulating brown adipogenesis partly through a mechanism involving cAMP activation and upregulation of miR-30b and miR-378.There are two specific types of fat with opposite functions, brown adipose tissue (BAT) 3 and white adipose tissue (WAT).WAT stores energy in the form of triglyceride, whereas BAT dissipates energy in the form of heat via uncoupling protein 1 (UCP1) (1). Recent advances in our understanding of BAT biology in humans have provided a new insight into weight loss strategies by boosting BAT thermogenesis. Despite the surge of research for identifying cellular and molecular regulators of brown fat development (2, 3), the role of dietary constituents, particularly dietary fatty acids (FA), in thermogenic activation is poorly understood. Depending on the degree of desaturation and the n-6/n-3 ratio, FA differentially control adiposity, insulin sensitivity, immune response (4), and probably energy expenditure (5-7). Lately, it has been suggested that n-3 polyunsaturated FA (PUFA) stimulate beige/brown adipogenesis in primary murine adipogenic precursor cells (5) as well as C57BL/6 mice (6, 7). The latter animal study suggests that n-3 PUFA are associated with sympathetic activation and increased ␤3-adrenergic receptor (Adrb3) signaling (7). However, the underlying mechanistic details of how dietary n-3 PUFA...

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Regulation of energy metabolism by long-chain fatty acids

Cited by 590 publications

References 259 publications

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-dependent Up-regulation of miR-30b and miR-378

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