Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

Luukkonen, Panu K.; Sädevirta, Sanja; Zhou, You; Kayser, Brandon D.; Ali, Ashfaq; Ahonen, Linda; Lallukka, Susanna; Pelloux, Véronique; Gaggini, Melania; Jian, Ching; Hakkarainen, Antti; Lundbom, Nina; Gylling, Helena; Salonen, Anne; Orešič, Matej; Hyötyläinen, Tuulia; Orho‐Melander, Marju; Rissanen, Aila; Gastaldelli, Amalia; Clément, Karine; Hodson, Leanne; Yki‐Järvinen, Hannele

doi:10.2337/dc18-0071

Cited by 285 publications

(326 citation statements)

References 40 publications

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“…qPCR has been widely used for accurate and targeted quantification of specific bacterial groups and species especially until the era of NGS. Here, we first quantified total bacteria using universal bacterial primers (12) by qPCR (Supplementary Methods) in 114 adult fecal DNA samples that have been analyzed for microbiota composition using Illumina MiSeq for 16S rRNA gene amplicon sequencing (13). The qPCR threshold cycle (Ct) values were converted to the estimates of bacterial genomes present in 1 g of feces (total bacterial counts), which were used to estimate absolute abundance of the NGS-detected taxa (Fig.…”

Section: Main Textmentioning

confidence: 99%

Quantitative PCR provides a simple and accessible method for quantitative microbiome profiling

Jian

Luukkonen

Yki‐Järvinen

et al. 2018

Preprint

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AbstractThe use of relative next generation sequencing (NGS) abundance data can lead to misinterpretations of microbial community structures as the increase of one taxon leads to concurrent decrease of the other(s). To overcome compositionality, we provide a quantitative NGS solution, which is achieved by adjusting the relative 16S rRNA gene amplicon NGS data with quantitative PCR (qPCR-based) total bacterial counts. By comparing the enumeration of dominant bacterial groups on different taxonomic levels in human fecal samples using taxon-specific 16S rRNA gene-targeted qPCR we show that quantitative NGS is able to estimate absolute bacterial abundances accurately. We also observed a higher degree of correspondence in the estimated microbe-metabolite relationship when quantitative NGS was applied. Being conceptually and methodologically analogous to amplicon-based NGS, our qPCR-based method can be readily incorporated into the standard, high-throughput NGS sample processing pipeline for more accurate description of interactions within and between the microbes and host.

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Section: Main Textmentioning

confidence: 99%

Quantitative PCR provides a simple and accessible method for quantitative microbiome profiling

Jian

Luukkonen

Yki‐Järvinen

et al. 2018

Preprint

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“…This would be of interest to do as the type of fat consumed appears to influence liver fat content as previously reviewed (42)(43)(44) . Taken together it has been found that diets overfeeding SFA increase liver fat content to a greater extent than diets overfeeding unsaturated (primarily monounsaturated and n-6 PUFA) fatty acids (45)(46)(47) . Supplementing the diet with n-3 fatty acids (namely EPA and DHA) at 4 g/d (as ethyl esters) for periods between 8 weeks and 16 months has also been reported to decrease liver fat (48)(49)(50) .…”

Section: Fatty Acid Sources: Dietarymentioning

confidence: 90%

“…Although these studies have investigated the effect of dietary fat quality on liver fat content, there is limited work investigating the effect on intra-hepatic fatty acid synthesis and partitioning. In the study by Luukkonen et al (47) it was found that fasting hepatic DNL was unchanged after 3 weeks overconsumption of SFA, whilst fasting hepatic DNL significantly increased after overconsumption of the carbohydrate-enriched diet. Rosqvist et al (46) over fed participants with SFA or n-6 PUFA and found no change in fasting plasma 3-OHB concentrations.…”

Section: Fatty Acid Sources: Dietarymentioning

confidence: 94%

Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state

Hodson

2018

Proc. Nutr. Soc.

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When we consume dietary fat, a series of complex metabolic processes ensures that fatty acids are absorbed, transported around the body and used/stored appropriately. The liver is a central metabolic organ within the human body and has a major role in regulating fat and carbohydrate metabolism. Studying hepatic metabolism in human subjects is challenging; the use of stable isotope tracers and measurement of particles or molecules secreted by the liver such as VLDL-TAG and 3-hydroxybutyrate offers the best insight into postprandial hepatic fatty acid metabolism in human subjects. Diet derived fatty acids are taken up by the liver and mix with fatty acids coming from the lipolysis of adipose tissue, and those already present in the liver (cytosolic TAG) and fatty acids synthesised de novo within the liver from non-lipid precursors (known as de novo lipogenesis). Fatty acids are removed from the liver by secretion as VLDL-TAG and oxidation. Perturbations in these processes have the potential to impact on metabolic health. Whether fatty acids are partitioned towards oxidation or esterification pathways appears to be dependent on a number of metabolic factors; not least ambient insulin concentrations. Moreover, along with the phenotype and lifestyle factors (e.g. habitual diet) of an individual, it is becoming apparent that the composition of the diet (macronutrient and fatty acid composition) may play pivotal roles in determining if intra-hepatic fat accumulates, although what remains to be elucidated is the influence these nutrients have on intra-hepatic fatty acid synthesis and partitioning. Liver: VLDL-TAG: Fatty acid partitioning: Fatty acid oxidationThe liver has a major role in regulating metabolic homeostasis; it is a central cross-road for fatty acid and glucose metabolism. It serves as an intermediary organ between dietary (exogenous) and endogenous energy sources and other extra-hepatic organs/tissues that consume energy; perturbations in its metabolism have the potential to impact widely on metabolic disease risk. In health, the liver rapidly adapts to alterations in nutritional state and the nutrient fluxes that occur from a fasted (postabsorptive) to fed (postprandial) state. However, the deposition of fat (ectopic fat) in nonadipose tissues such as the liver has been suggested to be an important factor in the development of obesity related metabolic abnormalities (1,2) . The net retention of intra-hepatic fat is a prerequisite for the development of non-alcoholic fatty liver disease (NAFLD) (3) , which is now recognised as the hepatic manifestation of the metabolic syndrome (2) . A well-recognised risk factor for NAFLD is obesity, and both are risk factors for more severe metabolic diseases such as type-2 diabetes and CVD; the prevalence of NAFLD parallels that of type-2 diabetes (4) . Why the liver starts to accumulate fat is not well understood but is likely to occur when fatty acid input and synthesis exceed the liver's capacity for removal (e.g. for secretion or oxidation) (5)(6)(7) . The intra-hepa...

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“…Saturated fat has been implicated in the pathogenesis of metabolic disease (15,16) and we have recently described and validated (using IMCL/EMCL simulated phantoms of known composition) a 1 H MRS method that provides an in vivo compositional marker of IMCL that primarily reflects the degree of saturation of the fatty acid chains within triglyceride (17). This marker, which we call the ‘IMCL saturation index’ (CH 2 :CH 3 ), utilizes good quality spectra acquired at 3T with short echo time and compares the CH 2 resonance located at 1.3 ppm (which is influenced by both concentration and composition), with that of the CH 3 resonance at 0.9 ppm which is independent of triglyceride composition: this is illustrated in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance spectroscopy analysis of intramyocellular lipid composition in lipodystrophic patients and athletes

Savage

Watson

Carr

et al. 2018

Preprint

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1 Context: Paradoxically, intramyocellular lipid (IMCL) accumulation has been linked to both 2 insulin-resistant and to insulin-sensitive (athletes) states. The composition of this lipid store is 3 unknown in these states. 4 Design and Methods:We used a recently validated and potentially widely applicable 1 H 5 magnetic resonance spectroscopy method to compare the compositional saturation index 6 (CH2:CH3 ratio) and concentration independent of composition (CH3) of intramyocellular 7 lipid in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic 8 patients with that of age-and gender-matched athletes (n=14) and healthy controls (n = 41). 9Main Outcome: IMCL compositional saturation index (CH2:CH3 ratio). 10

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Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

Cited by 285 publications

References 40 publications

Quantitative PCR provides a simple and accessible method for quantitative microbiome profiling

Quantitative PCR provides a simple and accessible method for quantitative microbiome profiling

Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state

Magnetic resonance spectroscopy analysis of intramyocellular lipid composition in lipodystrophic patients and athletes

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