Fructose stimulated de novo lipogenesis is promoted by inflammation

Todoric, Jelena; Di, Giuseppe; Reibe, Saskia; Henstridge, Darren C.; Green, Courtney R.; Vrbanac, Alison; Ceteci, Fatih; Conche, Claire; McNulty, Reginald; Shalapour, Shabnam; Taniguchi, Koji; Meikle, Peter J.; Watrous, Jeramie D.; Moranchel, Rafael; Najhawan, Mahan; Jain, Mohit; Liu, Xiao; Kisseleva, Tatiana; Diaz-Meco, Marı́a T.; Moscat, Jorge; Knight, Rob; Greten, Florian R.; Lau, Lester F.; Metallo, Christian M.; Febbraio, Mark A.; Karin, Michael

doi:10.1038/s42255-020-0261-2

Cited by 194 publications

(161 citation statements)

References 50 publications

(64 reference statements)

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“…Inflammatory signals activated MyD88 signaling in macrophages and subsequent TNF release. TNF then induced SREBF1 signaling in hepatocytes [100].…”

Section: De Novo Lipogenesismentioning

confidence: 97%

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Fructose Metabolism in Cancer

Krause

Wegner

2020

Cells

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The interest in fructose metabolism is based on the observation that an increased dietary fructose consumption leads to an increased risk of obesity and metabolic syndrome. In particular, obesity is a known risk factor to develop many types of cancer and there is clinical and experimental evidence that an increased fructose intake promotes cancer growth. The precise mechanism, however, in which fructose induces tumor growth is still not fully understood. In this article, we present an overview of the metabolic pathways that utilize fructose and how fructose metabolism can sustain cancer cell proliferation. Although the degradation of fructose shares many of the enzymes and metabolic intermediates with glucose metabolism through glycolysis, glucose and fructose are metabolized differently. We describe the different metabolic fates of fructose carbons and how they are connected to lipogenesis and nucleotide synthesis. In addition, we discuss how the endogenous production of fructose from glucose via the polyol pathway can be beneficial for cancer cells.

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“…Inflammatory signals activated MyD88 signaling in macrophages and subsequent TNF release. TNF then induced SREBF1 signaling in hepatocytes [100].…”

Section: De Novo Lipogenesismentioning

confidence: 97%

“…A recent study shows both the carbon contribution as well as signaling effect of fructose in hepatic DNL [100]. In transgenic mice, a high-fructose diet led to higher cytosolic acetyl-CoA pool, increased liver triglycerides, and increased expression of SREBF1, ChREBP, ACC1, and FASN.…”

Section: De Novo Lipogenesismentioning

confidence: 98%

Fructose Metabolism in Cancer

Krause

Wegner

2020

Cells

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“…Digested food effects the function, community, and structure of the gut microbiota that can improve or deteriorate the host's health. Intakes of fructose is specifically linked to gut flora dysbiosis [5,6], which suggests that the fatty liver could be mediated by some gut microbiome [4,7,8]. Xue et al reported showed that the critical microbial products lipopolysaccharides (LPS) are involved in the pathogenesis of NAFLD [9].…”

Section: Introductionmentioning

confidence: 99%

Co-Treatment with Cefotaxime and High-Fructose Diet Inducing Nonalcoholic Fatty Liver Disease and Gut Microbial Dysbiosis in Mice

et al. 2021

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High fructose diet causes metabolic syndrome and induces host gut microbial dysbiosis and related obesity and nonalcoholic fatty liver disease (NAFLD). Several antibiotic treatments could prevent fatty liver. However, there are studies that have demonstrated that a high-fructose diet could influence the gut microbial dysbiosis and induce fatty liver. The purpose of this study was performed to partially modify the gut bacterial composition with a single cefotaxime treatment, which might affect the fructose-induced NAFLD severity. The C57BL/6JNarl male mice were divided into four groups including vehicle/chow diet (VE-CD), vehicle/high-fructose diet (VE-FD), antibiotic (cefotaxime (CF))/CD, and CF/FD. The results showed that body weight gain, moderate hepatic steatosis severity, epididymal white adipose tissue hypertrophy, and insulin resistance occurrence with NAFLD-related symptoms were observed only in the CF-FD group. The raised protein expression of hepatic lipogenesis was observed in the CF-FD group, but lipolysis protein expression was no difference. The diversity and composition of microbiota were significantly reduced in the CF-FD group. The Erysipelatoclostridium, Enterobacteriaceae, Lachnospiraceae, and Escherichia Shigella were in increased abundance in the feces of CF-FD group compared with VE-FD group. The novel model reveals that particular antibiotics such as cefotaxime co-treatment with high-fructose diet may affect the gut microbiota accelerating the NAFLD and obesity.

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“…Previous reports also highlighted that dietary free sugars damaged gut microbiome and promoted colitis in mice. Free sugars, fructose in particular, were demonstrated to disrupt the gut-liver axis, possibly through increased gut permeability and altered gut microbiota [13,14]. Although it is widely accepted that intake of fruit has health bene t in human and is correlated with decreased risk of cardiovascular disease and some cancers, recently, a large-scale population-based prospective cohort study showed that the consumption of sugary drinks, even pure fruit juices, was positively associated with the increased risk of overall cancer [15].…”

Section: Introductionmentioning

confidence: 99%

Excessive Intake of Longan Arillus Alters Gut Homeostasis and Aggravates Colitis in Mice

Wang

et al. 2020

Preprint

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BackgroundLongan is the fruit of Dimocarpus longan Lour. and the longan arillus has been used in traditional Chinese medicine for thousands of years possessing various health benefits. However, the excessive intake of longan is found in daily life to cause “shanghuo” syndrome. Shanghuo has been linked to increased disease susceptibility. The present study thus aimed to investigate the toxicological outcomes after excess longan treatment.MethodsLongan extract at a normal dosage of 4 g/kg and two excess dosages of 8 and 16 g/kg was orally administered to normal C57BL/6J mice for 2 weeks. Another set of study used C57BL/6J mice with dextran sulfate sodium (DSS)-induced colitis by giving mice drinking water containing 3.5% DSS for 5 consecutive days. Mouse feces were collected at the end of experiments for microbial analysis by 16S rRNA sequencing. After mice were sacrificed, colonic contents were collected for measurement of short-chain fatty acid (SCFA) contents. Colon tissue was used for histopathological observation after H&E staining, detection of ZO-1 protein expression by western blot, analysis of TNF-α and IL-6 gene expression, and detection of apoptotic cells by TUNEL assay. Serum was collected for analysis of LPS, TNF-α and IL-6 by ELISA method.ResultsIn normal mice, repeated longan intake at excess doses, but not the normal dose, increased infiltration of inflammatory cells, elevated serum levels of TNF-α and IL-6 and reduced production of SCFAs. In DSS-induced colitic mice, longan intake at 4 g/kg did not promoted colitis in mice, while excess longan (8 or 16 g/kg) enhanced colitis in mice, showing increased inflammation (shorter colon length, upregulated IL-1β and TNF-α), more serious histological abnormalities, increased gut permeability (decreased ZO-1 protein expression), and increased epithelia injury (increased TUNEL-positive cells) when compared to DSS alone. Excess longan induced a significant reduction of microbial diversity in colitic mice, accompanied with aggravated alterations of DSS-associated bacteria including the increase of Proteobacteria phylum and genera of Bacteroides, Akkermansia, Turicibacter and Escherchia-Shigella, and the decrease of norank_f__Muribaculaceae. The changed microbial compositions were accompanied with decreased SCFAs when longan was supplemented with DSS. The altered microbial communities and SCFAs were tightly correlated with aggravated colon injury in mice.ConclusionsExcess longan intake disturbs gut homeostasis and aggravates colitis via promoting inflammation and altering gut microbe compositions and associated metabolism in mice. Our findings warrant rational longan arillus consumption as a dietary supplement among general population and suggest contraindications such as inflammatory bowel disease of using longan as an herbal medicine.

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Fructose stimulated de novo lipogenesis is promoted by inflammation

Cited by 194 publications

References 50 publications

Fructose Metabolism in Cancer

Fructose Metabolism in Cancer

Co-Treatment with Cefotaxime and High-Fructose Diet Inducing Nonalcoholic Fatty Liver Disease and Gut Microbial Dysbiosis in Mice

Excessive Intake of Longan Arillus Alters Gut Homeostasis and Aggravates Colitis in Mice

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