A Neural basis for Octanoic acid regulation of energy balance

Haynes, Vanessa; Michael, Natalie J.; Top, M. van den; Zhao, Fengshu; Brown, Russell D.; Souza, David de; Dodd, Garron T.; Spanswick, David; Watt, Matthew J.

doi:10.1016/j.molmet.2020.01.002

Cited by 25 publications

(22 citation statements)

References 69 publications

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“…Free fatty acids can penetrate the blood–brain barrier and act as modulators on multiple target sites by binding to fatty acid-binding receptors. Different length chain fatty acids have been reported to mitigate adipocyte dysfunction and glucose uptake . Additionally, many studies have shown that probiotics induce brown-fat-like signatures in white adipocytes and also inhibit adipocyte differentiation by regulating various signaling factors. ,, In this study, we demonstrated that B.…”

Section: Discussionmentioning

confidence: 55%

“…Different length chain fatty acids have been reported to mitigate adipocyte dysfunction and glucose uptake. 31 Additionally, many studies have shown that probiotics induce brown-fat-like signatures in white adipocytes and also inhibit adipocyte differentiation by regulating various signaling factors. 18,19,22 In this study, we demonstrated that B. longum subsp.…”

Section: ■ Discussionmentioning

confidence: 99%

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Bifidobacterium longum subsp. infantis YB0411 Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes and Reduces High-Fat-Diet-Induced Obesity in Mice

Rahman

Kang

Lee

et al. 2021

J. Agric. Food Chem.

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Although the health benefits of probiotics have been widely known for decades, there has still been limited use of probiotic bacteria in anti-obesity therapy. Herein, we demonstrated the role of Bifidobacterium longum subsp. infantis YB0411 (YB, which was selected by an in vitro adipogenesis assay) in adipogenic differentiation in 3T3-L1 pre-adipocytes. We observed that YB-treatment effectively reduced triglyceride accumulation and the expression of CCAAT/enhancer-binding protein α, β, and δ (C/EBPα, C/EBPβ, and C/EBPδ), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (aP2), and acetyl-CoA carboxylase (ACC). YB-treatment also reduced the levels of core autophagic markers (p62 and LC3B) in 3T3-L1 pre-adipocytes. Small-interfering-RNA-mediated knockdown and competitive-chemical-inhibition assays showed that AMP-activated protein kinase (AMPK) commenced the anti-adipogenic effect of YB. In addition, YB supplement markedly reduced body weight and fat accretion in mice with high-fat-diet-induced obesity. Our findings suggest that YB may be used as a potential probiotic candidate to ameliorate obesity.

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Section: Discussionmentioning

confidence: 55%

Section: ■ Discussionmentioning

confidence: 99%

Bifidobacterium longum subsp. infantis YB0411 Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes and Reduces High-Fat-Diet-Induced Obesity in Mice

Rahman

Kang

Lee

et al. 2021

J. Agric. Food Chem.

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“…Furthermore, C10 also has a larger membrane permeability than C8, due to the longer carbon chain, which increases diffusion across the cell and mitochondrial membranes [ 40 ], which may also contribute to the observed preferential metabolism of C10 over C8. Although astrocytes are the main cellular compartment of MCFA metabolism, it was recently demonstrated that a subset of neurons in the hypothalamus have a large capacity for C8 oxidation [ 49 ]. In these hypothalamic neurons, C8 metabolism regulate neuronal excitability and food intake, which underlines the complexity and importance of regional brain energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte metabolism of the medium-chain fatty acids octanoic acid and decanoic acid promotes GABA synthesis in neurons via elevated glutamine supply

et al. 2021

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The medium-chain fatty acids octanoic acid (C8) and decanoic acid (C10) are gaining attention as beneficial brain fuels in several neurological disorders. The protective effects of C8 and C10 have been proposed to be driven by hepatic production of ketone bodies. However, plasma ketone levels correlates poorly with the cerebral effects of C8 and C10, suggesting that additional mechanism are in place. Here we investigated cellular C8 and C10 metabolism in the brain and explored how the protective effects of C8 and C10 may be linked to cellular metabolism. Using dynamic isotope labeling, with [U-13C]C8 and [U-13C]C10 as metabolic substrates, we show that both C8 and C10 are oxidatively metabolized in mouse brain slices. The 13C enrichment from metabolism of [U-13C]C8 and [U-13C]C10 was particularly prominent in glutamine, suggesting that C8 and C10 metabolism primarily occurs in astrocytes. This finding was corroborated in cultured astrocytes in which C8 increased the respiration linked to ATP production, whereas C10 elevated the mitochondrial proton leak. When C8 and C10 were provided together as metabolic substrates in brain slices, metabolism of C10 was predominant over that of C8. Furthermore, metabolism of both [U-13C]C8 and [U-13C]C10 was unaffected by etomoxir indicating that it is independent of carnitine palmitoyltransferase I (CPT-1). Finally, we show that inhibition of glutamine synthesis selectively reduced 13C accumulation in GABA from [U-13C]C8 and [U-13C]C10 metabolism in brain slices, demonstrating that the glutamine generated from astrocyte C8 and C10 metabolism is utilized for neuronal GABA synthesis. Collectively, the results show that cerebral C8 and C10 metabolism is linked to the metabolic coupling of neurons and astrocytes, which may serve as a protective metabolic mechanism of C8 and C10 supplementation in neurological disorders.

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“…However, in addition to the effects of their metabolites (i.e., ketones), C8 and C10 have been shown to directly improve neural function. For instance, C8 regulates the energy balance by affecting the activity of pro-opiomelanocortin neurons [( 28 ) (Sec3.4)]; C10 enhances mitochondrial function in neurons by activating the SIRT1 enzyme [( 29 ) (Sec3.3.2)] and regulates astrocyte function by inhibiting mTOR [( 30 ) (R12, F7)]; and both C8 and C10 increase neuronal GABA synthesis by increasing the glutamine supply [( 31 ) (R5, F5)]. Thus, the optimal dose and composition of MCTs may differ from previous recommendations and from those provided hereafter in the light of other relevant factors.…”

Section: Discussionmentioning

confidence: 99%

The Ketogenic Effect of Medium-Chain Triacylglycerides

2021

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Medium-chain triacylglycerides (MCTs) are dietary supplements that can induce ketosis without the need for a traditional ketogenic diet or prolonged fasting. They have the potential to marginally delay the progression of neurodegenerative diseases, such as Alzheimer's disease. However, there have been inconsistencies in reports of the MCT dose–response relationship, which may be due to differences in MCT composition, participant characteristics, and other factors that can influence ketone generation. To resolve these discrepancies, we reviewed studies that investigated the ketogenic effect of MCTs in healthy adults. Aside from the treatment dose, other factors that can influence the ketogenic response, such as accompanying meals, fasting duration, and caffeine intake, were assessed. Based on the available literature, four practical recommendations are made to optimize the ketogenic effect of MCTs and reduce unwanted side effects (primarily gastrointestinal discomfort and diarrhea). First, the starting dose should be either 5 g of octanoic acid [caprylic acid (C8); a component of MCTs] or 5 g of a combination of C8 and decanoic or capric acid (C10; another component of MCTs), and the dose should be progressively increased to 15–20 g of C8. Second, MCTs should be consumed after an overnight fast, without an accompanying meal if tolerable, or with a low-carbohydrate meal. Third, the addition of caffeine may slightly increase the ketogenic response. Fourth, emulsifying the MCTs might increase their ketogenic effect and alleviate side effects.

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A Neural basis for Octanoic acid regulation of energy balance

Cited by 25 publications

References 69 publications

Bifidobacterium longum subsp. infantis YB0411 Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes and Reduces High-Fat-Diet-Induced Obesity in Mice

Bifidobacterium longum subsp. infantis YB0411 Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes and Reduces High-Fat-Diet-Induced Obesity in Mice

Astrocyte metabolism of the medium-chain fatty acids octanoic acid and decanoic acid promotes GABA synthesis in neurons via elevated glutamine supply

The Ketogenic Effect of Medium-Chain Triacylglycerides

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