Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans

Lundsgaard, Anne‐Marie; Fritzen, Andreas M.; Sjøberg, Kim A.; Kleinert, Maximilian; Richter, Erik A.

doi:10.2337/db20-0582

Cited by 21 publications

(16 citation statements)

References 40 publications

(36 reference statements)

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“…Coconut oil and C12:0 also failed to induce insulin resistance to the degree that various comparator oils/fats do in rodent models 27,57,58 . Protective cardiometabolic effects of C12:0 in human feeding trials 28 and epidemiological 30 29 investigations, relative to longer-chain saturated fats, have also begun to emerge. Pleiotropic effects of C12:0 through LRH-1 signaling, which has well-described roles in glucose sensing and whole body cholesterol regulation, protecting against insulin resistance 61 , beta cell dysfunction 62,63 , and atherosclerosis 64 , remains speculative but plausible mechanism by which C12:0, and by extension, C12:0-rich oils such as palm kernel oil and coconut oil, may have diverse impacts on cardiometabolic health.…”

Section: Discussionmentioning

confidence: 99%

“…Despite increases in risk factors, particularly LDL, preclinical rodent models employing coconut oil have failed to observe expected atherogenic 25,26 and diabetogenic 27 phenotypes. Both clinical trial 28 and observational epidemiological investigations 29,30 have suggested beneficial cardiometabolic effects of C12:0 relative to other saturated fatty acids. Such observations are consistent with pleiotropic effects of C12:0, though few have been described to date, apart from C12:0’s relative high oxidation rate in vivo 31 and ability to activate toll-like receptors at high concentrations in vitro 32–34 .…”

Section: Introductionmentioning

confidence: 99%

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LRH-1 NUTRIGENOMICS: The Provision of Lauric Acid Results in the Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and LRH-1 Transactivation

Klatt

Zhang

Malysheva

et al. 2021

Preprint

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BackgroundThe unusual phosphatidylcholine species, dilauroylphosphatidylcholine (DLPC), has been reported to bind and activate the orphan nuclear receptor, liver receptor homolog-1 (LRH-1). To date, DLPC has not been reported endogenously in metabolomic databases.ObjectiveHerein, we test the hypothesis that the provision of the acyl constituent of DLPC, lauric acid (C12:0), a saturated fatty acid rich in tropical oils such as coconut oil, will 1) result in endogenous DLPC production and 2) enhance LRH-1 transcriptional activity.MethodsWe measured DLPC following provision of C12:0 to HepG2 cells, C57/BL6J mice, and to healthy human participants in an acute, randomized, controlled cross-over trial. LRH-1fl/fl and LRH-1fl/fl Albumin-Cre mice were used in ex vivo and in vivo approaches. to assess the impact of C12:0 on LRH-1 target gene expression. 1-13C-lauric acid and methyl-d9-choline were used to assess DLPC production dynamics.ResultsDLPC was not observed in any C12:0-free approach. Provision of C12:0 in the culture media or to C57/BL6J mice resulted in the rapid production of DLPC, including DLPC’s presence in multiple LRH-1 expressing tissues. Coconut oil-fed human participants exhibited DLPC in postprandial serum samples. Ex vivo and in vivo C12:0 provision resulted in increased mRNA expression of LRH-1 target genes, an effect that was not observed in hepatic knockout mice. Methyl-d9-choline administration revealed a complex reliance on CDP-choline-derived DLPC.ConclusionC12:0 provision results in endogenous production of the LRH-1 ligand, DLPC, and LRH-1 transcriptional activation phenotypes. Our findings highlight pleiotropic effects of lauric acid, a common hypercholesterolemic dietary saturated fatty acid, secondary to LRH-1 agonism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LRH-1 NUTRIGENOMICS: The Provision of Lauric Acid Results in the Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and LRH-1 Transactivation

Klatt

Zhang

Malysheva

et al. 2021

Preprint

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“…In addition, butanoic acid fits the new definition of prebiotics [38,39]. Among medium chain fatty acids, they all bear health-related attributes [40,41], but some have unpleasant off-odors. For example, nonanoic acid may represent a marker compound of hemp seed product, owning a typical scent [10,35], hexanoic and octanoic acids possess rancid-like traits [42,43] and their concentrations should be modulated in the food product.…”

Section: Organic Acidsmentioning

confidence: 98%

The Exploitation of a Hempseed Byproduct to Produce Flavorings and Healthy Food Ingredients by a Fermentation Process

et al. 2021

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Following the One Health principles in food science, the challenge to valorize byproducts from the industrial sector is open. Hemp (Cannabis sativa subsp. sativa) is considered an important icon of sustainability and as an alternative food source. Hemp seed bran, in particular, is a byproduct of industrial hemp seed processing, which is not yet valorized. The success, and a wider market diffusion of hemp seed for food applications, is hindered by its unpleasant taste, which is produced by certain compounds that generally overwhelm the pleasant bouquet of the fresh product. This research concerns the exploration of hemp seed bran through fermentation using beneficial lactobacilli, focusing on the sensorial and bioactive traits of the products when they are subjected to bacterial transformation. By studying of the aromatic profile formation during the fermentation process the aim was to modulate it in order to reduce off-odors without affecting the presence of healthy volatile organic compounds (VOCs). Applying multivariate analyses, it was possible to target the contribution of processing parameters to the generation of flavoring and bioactive compounds. To conclude, the fermentation process proposed was able to reduce unpleasant VOCs, whilst at the same time keeping the healthy ones, and it also improved nutritional quality, depending on time and bacterial starters. The fermentation proposed was a sustainable biotechnological approach that fitted perfectly with the valorization of hemp byproducts from the perspective of a green-oriented industrial process that avoids synthetic masking agents.

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“…Possibly, this effect could be due to the PRF compounds of Eco4%, as other authors reported that these species are able to hydrolyze oleuropein, a polyphenol rich in olive oil, to form hydroxycortisol acetate [29,56]. Medium-Chain Fatty Acids (MCFAs) have protective effects on glucose homeostasis during high-fat overfeeding and against insulin resistance [57] and are important metabolic biomarkers of dysbiosis associate to Intestinal Bowel Disease (IBD) [28,58]. MCFAs' concentration increased after fermentation with FOS or Eco4% compared to baseline (Figure 3B and Table S2).…”

Section: Changes In Main Microbial Metabolites Related To Prebiotic Potentialmentioning

confidence: 99%

Colonic In Vitro Model Assessment of the Prebiotic Potential of Bread Fortified with Polyphenols Rich Olive Fiber

et al. 2021

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The use of olive pomace could represent an innovative and low-cost strategy to formulate healthier and value-added foods, and bakery products are good candidates for enrichment. In this work, we explored the prebiotic potential of bread enriched with Polyphenol Rich Fiber (PRF), a defatted olive pomace byproduct previously studied in the European Project H2020 EcoProlive. To this aim, after in vitro digestion, the PRF-enriched bread, its standard control, and fructo-oligosaccharides (FOS) underwent distal colonic fermentation using the in vitro colon model MICODE (multi-unit colon gut model). Sampling was done prior, over and after 24 h of fermentation, then metabolomic analysis by Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (SPME GCMS), 16S-rDNA genomic sequencing of colonic microbiota by MiSeq, and absolute quantification of main bacterial species by qPCR were performed. The results indicated that PRF-enriched bread generated positive effects on the host gut model: (i) surge in eubiosis; (ii) increased abundance of beneficial bacterial groups, such as Bifidobacteriaceae and Lactobacillales; (iii) production of certain bioactive metabolites, such as low organic fatty acids; (iv) reduction in detrimental compounds, such as skatole. Our study not only evidenced the prebiotic role of PRF-enriched bread, thereby paving the road for further use of olive by-products, but also highlighted the potential of the in vitro gut model MICODE in the critical evaluation of functionality of food prototypes as modulators of the gut microbiota.

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Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans

Abstract: Running title: Medium-versus long-chain fatty acids and insulin action.

Cited by 21 publications

References 40 publications

LRH-1 NUTRIGENOMICS: The Provision of Lauric Acid Results in the Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and LRH-1 Transactivation

LRH-1 NUTRIGENOMICS: The Provision of Lauric Acid Results in the Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and LRH-1 Transactivation

The Exploitation of a Hempseed Byproduct to Produce Flavorings and Healthy Food Ingredients by a Fermentation Process

Colonic In Vitro Model Assessment of the Prebiotic Potential of Bread Fortified with Polyphenols Rich Olive Fiber

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