Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease

Buziau, Amée M.; Schalkwijk, Casper G.; Stehouwer, Coen D. A.; Tolan, Dean R.; Brouwers, Martijn C.G.J.

doi:10.1007/s00018-019-03348-2

Cited by 40 publications

(38 citation statements)

References 95 publications

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“…The discrepancy between ALDOB mRNA and protein expression might be due to a high translation efficiency or because of the posttranscriptional modification of aldolase B protein 30 . The latter regulates the activity of aldolase and thus rates of glycolysis/gluconeogenesis, the pentose phosphate pathway, and fructose and mannose metabolism 31 . In addition to its function in glycolysis, GAPDH has important roles in DNA repair and replication, post transcriptional regulation, gene expression, and cell death 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Jejunal mucosa proteomics unravel metabolic adaptive processes to mild chronic heat stress in dairy cows

Koch

Albrecht

Görs

et al. 2021

Sci Rep

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Climate change affects the duration and intensity of heat waves during summer months and jeopardizes animal health and welfare. High ambient temperatures cause heat stress in dairy cows resulting in a reduction of milk yield, feed intake, and alterations in gut barrier function. The objectives of this study were to investigate the mucosal amino acid, glucose and lactate metabolism, as well as the proteomic response of the small intestine in heat stressed (HS) Holstein dairy cows. Cows of the HS group (n = 5) were exposed for 4 days to 28 °C (THI = 76) in a climate chamber. Percentage decrease in daily ad libitum intake of HS cows was calculated to provide isocaloric energy intake to pair-fed control cows kept at 15 °C (THI = 60) for 4 days. The metabolite, mRNA and proteomic analyses revealed that HS induced incorrect protein folding, cellular destabilization, increased proteolytic degradation and protein kinase inhibitor activity, reduced glycolysis, and activation of NF-κB signaling, uronate cycling, pentose phosphate pathway, fatty acid and amino acid catabolism, mitochondrial respiration, ATPase activity and the antioxidative defence system. Our results highlight adaptive metabolic and immune mechanisms attempting to maintain the biological function in the small intestine of heat-stressed dairy cows.

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Section: Discussionmentioning

confidence: 99%

Jejunal mucosa proteomics unravel metabolic adaptive processes to mild chronic heat stress in dairy cows

Koch

Albrecht

Görs

et al. 2021

Sci Rep

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“…In man, autosomal recessive loss-of-function mutations in the KHK gene resulting in ketohexokinase deficiency, manifest as a benign condition “essential fructosuria” in which fructose is excreted in the urine because of impaired hepatic clearance ( 81 ) and likewise in mice Khk deletion has negligible phenotype ( 82 ) and in conjunction with AldB deficiency is protective ( 83 ). Loss-of-function mutations in AldB cause hereditary fructose intolerance, a severe condition which manifests as acute liver damage with ATP depletion and hyperuricaemia on consumption of fructose, leading to liver failure ( 84 ). Two hypotheses can be considered for the protective effect of ChREBP in conjunction with a high-fructose diet.…”

Section: The Fructose and Glucokinase Activator Paradoxesmentioning

confidence: 99%

“…Two hypotheses can be considered for the protective effect of ChREBP in conjunction with a high-fructose diet. First, that ChREBP deficiency results in greater impairment of AldB and Tkfc relative to Khk and Slc2a5 thereby mimicking AldB or Tkfc deficiency ( 66 , 84 ). Second, that other ChREBP target genes such as Pklr , G6pc and Gckr have an overriding role in the adaptive response to fructose.…”

Section: The Fructose and Glucokinase Activator Paradoxesmentioning

confidence: 99%

The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective

2020

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The Carbohydrate response element binding protein, ChREBP encoded by the MLXIPL gene, is a transcription factor that is expressed at high levels in the liver and has a prominent function during consumption of high-carbohydrate diets. ChREBP is activated by raised cellular levels of phosphate ester intermediates of glycolysis, gluconeogenesis and the pentose phosphate pathway. Its target genes include a wide range of enzymes and regulatory proteins, including G6pc , Gckr , Pklr, Prkaa1,2 , and enzymes of lipogenesis. ChREBP activation cumulatively promotes increased disposal of phosphate ester intermediates to glucose, via glucose 6-phosphatase or to pyruvate via glycolysis with further metabolism by lipogenesis. Dietary fructose is metabolized in both the intestine and the liver and is more lipogenic than glucose. It also induces greater elevation in phosphate ester intermediates than glucose, and at high concentrations causes transient depletion of inorganic phosphate, compromised ATP homeostasis and degradation of adenine nucleotides to uric acid. ChREBP deficiency predisposes to fructose intolerance and compromised cellular phosphate ester and ATP homeostasis and thereby markedly aggravates the changes in metabolite levels caused by dietary fructose. The recent evidence that high fructose intake causes more severe hepatocyte damage in ChREBP-deficient models confirms the crucial protective role for ChREBP in maintaining intracellular phosphate homeostasis. The improved ATP homeostasis in hepatocytes isolated from mice after chronic activation of ChREBP with a glucokinase activator supports the role of ChREBP in the control of intracellular homeostasis. It is hypothesized that drugs that activate ChREBP confer a protective role in the liver particularly in compromised metabolic states.

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“…The development of fructose intolerance is closely related to abnormal expression and function of the enzymes critically involved in fructose absorption and metabolism. [ 28 ] Hereditary fructose intolerance, caused by catalytic deficiency of aldolase B, results in a serious defect of fructose metabolism along with an severe accumulation of F-1-P, which leads to hypoglycemic and severe abdominal symptoms as well as liver and kidney injury after fructose consumption. [ 29 ] Another hereditary fructose intolerance is related to fructose bisphosphatase 1 (FBP1), which has long been recognized as a key component to control the rate of hepatic gluconeogenesis in response to energy status.…”

Section: Fructose Metabolism and Homeostasismentioning

confidence: 99%

Fructose and metabolic diseases: too much to be good

Shi

Liu

Xie

et al. 2021

Chinese Medical Journal

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Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element–binding protein in regulating fructose metabolism.

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Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease

Cited by 40 publications

References 95 publications

Jejunal mucosa proteomics unravel metabolic adaptive processes to mild chronic heat stress in dairy cows

Jejunal mucosa proteomics unravel metabolic adaptive processes to mild chronic heat stress in dairy cows

The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective

Fructose and metabolic diseases: too much to be good

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