Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs

Tappy, Luc

doi:10.1016/j.clnu.2020.12.022

Cited by 31 publications

(36 citation statements)

References 71 publications

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“…Sucrose and high-fructose corn syrup are both composed of near-equal amounts of glucose and fructose. There is rising evidence that in these sweeteners, fructose and, in a lesser extent, glucose favor the development of metabolic diseases associated with sugar intake (7)(8)(9)(10). Obesity-associated chronic low-grade inflammation characterized by high levels of plasmatic inflammatory markers [C-reactive protein, interleukin 6 (IL6) or tumor necrosis factor a (TNFa)] largely contributes to the development of the obesityrelated chronic metabolic diseases (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

et al. 2021

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A causal correlation between the metabolic disorders associated with sugar intake and disruption of the gastrointestinal (GI) homeostasis has been suggested, but the underlying mechanisms remain unclear. To unravel these mechanisms, we investigated the effect of physiological amounts of fructose and glucose on barrier functions and inflammatory status in various regions of the GI tract and on the cecal microbiota composition. C57BL/6 mice were fed chow diet and given 15% glucose or 15% fructose in drinking water for 9 weeks. We monitored caloric intake, body weight, glucose intolerance, and adiposity. The intestinal paracellular permeability, cytokine, and tight junction protein expression were assessed in the jejunum, cecum, and colon. In the cecum, the microbiota composition was determined. Glucose-fed mice developed a marked increase in total adiposity, glucose intolerance, and paracellular permeability in the jejunum and cecum while fructose absorption did not affect any of these parameters. Fructose-fed mice displayed increased circulation levels of IL6. In the cecum, both glucose and fructose intake were associated with an increase in Il13, Ifnγ, and Tnfα mRNA and MLCK protein levels. To clarify the relationships between monosaccharides and barrier function, we measured the permeability of Caco-2 cell monolayers in response to IFNγ+TNFα in the presence of glucose or fructose. In vitro, IFNγ+TNFα-induced intestinal permeability increase was less pronounced in response to fructose than glucose. Mice treated with glucose showed an enrichment of Lachnospiracae and Desulfovibrionaceae while the fructose increased relative abundance of Lactobacillaceae. Correlations between pro-inflammatory cytokine gene expression and bacterial abundance highlighted the potential role of members of Desulfovibrio and Lachnospiraceae NK4A136 group genera in the inflammation observed in response to glucose intake. The increase in intestinal inflammation and circulating levels of IL6 in response to fructose was observed in the absence of intestinal permeability modification, suggesting that the intestinal permeability alteration does not precede the onset of metabolic outcome (low-grade inflammation, hyperglycemia) associated with chronic fructose consumption. The data also highlight the deleterious effects of glucose on gut barrier function along the GI tract and suggest that Desulfovibrionaceae and Lachnospiraceae play a key role in the onset of GI inflammation in response to glucose.

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Section: Introductionmentioning

confidence: 99%

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

et al. 2021

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“…Differential functional pathway analysis of the gut microbiota revealed that fructose and mannose metabolism was significantly enriched in mice fed high-AGE diets. Excess fructose can lead to insulin resistance and metabolic syndrome, 42 and Jaiswal et al 43 reported that fructose- This study has several limitations. First, we confirmed the association between gut bacteria (especially butyrateproducing bacteria) and insulin resistance, exclusively in mice fed high-AGE diets.…”

Section: Discussionmentioning

confidence: 87%

“…Differential functional pathway analysis of the gut microbiota revealed that fructose and mannose metabolism was significantly enriched in mice fed high-AGE diets. Excess fructose can lead to insulin resistance and metabolic syndrome, 42 and Jaiswal et al 43 reported that fructose-induced generation of reactive oxygen species impairs glucose utilization and insulin signaling in skeletal muscle cells. In the present study, fructose metabolism may have altered glucose homeostasis, resulting in insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Dietary Advanced Glycation End Products Shift the Gut Microbiota Composition and Induce Insulin Resistance in Mice

Wang¹,

Cai²,

Yu³

et al. 2022

DMSO

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This study aimed to explore the associations between gut microbiota characteristics and glycometabolic profiles in mice fed diets high in advanced glycation end products (AGEs). Methods: C57BL/6 mice were exposed to a heat-treated diet or exogenous AGEs for 24 weeks, and glucose metabolism was assessed via the intraperitoneal glucose-tolerance test (IPGTT). Serum AGE and lipopolysaccharide-binding protein (LBP) levels were quantified using ELISA kits. 16S rDNA sequencing was performed to analyze the changes in gut microbiota according to α-and βdiversity. Key operational taxonomic units (OTUs) were evaluated, and co-abundance groups (CAGs) were delineated using weighted correlation network analysis. Associations between CAGs and clinical parameters were analyzed using Spearman correlation; predictive functional analysis of gut microbiota was performed using Kyoto Encyclopedia of Genes and Genomes data. Results: We identified significant increases in fasting blood glucose (FBG) and fasting insulin levels, as well as homeostatic model assessment insulin resistance (HOMA-IR) and glucose area under the receiver operating characteristic curve from IPGTT, in the high-AGE diet groups relative to controls at week 24. Serum AGE and LBP levels were elevated, and the α-and β-diversity of gut microbiota reduced in high-AGE diet groups. We identified 92 key OTUs that clustered into six CAGs, revealing positive correlations between CAG2/3/5 and insulin levels and mice weight and negative correlations between CAG1/3/4/5 and AGE, FBG, and LBP levels and HOMA-IR in mice fed high-AGE diets. We observed a reduced abundance of butyrate-producing bacteria, including Bacteroidales_S24-7, Ruminococcaceae, and Lachnospiraceae, in mice fed high-AGE diets, with pathway analysis of gut microbiota revealing significantly enriched fructose and mannose metabolism. Conclusion: High-AGE diets altered the gut microbiota composition and structure, and induced insulin resistance in mice. In the pathogenesis of insulin resistance, the loss of butyrate-producing bacteria might impair the colonic epithelial barrier, thereby triggering chronic low-grade inflammation.

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“…The liver is a metabolic organ that is responsible for glucose and lipid homeostasis, drug metabolism, and bile synthesis ( Diehl-Jones and Askin, 2002 ; Almazroo et al, 2017 ; Tappy, 2021 ). Liver diseases contain non-alcoholic fatty liver disease (NAFLD) and its related diseases, drugs or infections induced liver injury, liver cancer, and among others.…”

Section: Introductionmentioning

confidence: 99%

Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms

Xie

Wang

et al. 2022

Front. Pharmacol.

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The liver plays an important role in glucose and lipid homeostasis, drug metabolism, and bile synthesis. Metabolic disorder and inflammation synergistically contribute to the pathogenesis of numerous liver diseases, such as metabolic-associated fatty liver disease (MAFLD), liver injury, and liver cancer. Celastrol, a triterpene derived from Tripterygium wilfordii Hook.f., has been extensively studied in metabolic and inflammatory diseases during the last several decades. Here we comprehensively review the pharmacological activities and the underlying mechanisms of celastrol in the prevention and treatment of liver diseases including MAFLD, liver injury, and liver cancer. In addition, we also discuss the importance of novel methodologies and perspectives for the drug development of celastrol. Although celastrol has been claimed as a promising agent against several metabolic diseases, both preclinical and clinical studies are highly required to accelerate the clinical transformation of celastrol in treating different liver illness. It is foreseeable that celastrol-derived therapeutics is evolving in the field of liver ailments.

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Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs

Cited by 31 publications

References 71 publications

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

Dietary Advanced Glycation End Products Shift the Gut Microbiota Composition and Induce Insulin Resistance in Mice

Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms

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