Fructose-derived advanced glycation end-products drive lipogenesis and skeletal muscle reprogramming via SREBP-1c dysregulation in mice

Mastrocola, Raffaella; Nigro, Debora; Chiazza, Fausto; Medana, Claudio; Bello, Federica Dal; Boccuzzi, Giuseppe; Collino, Massimo; Aragno, Manuela

doi:10.1016/j.freeradbiomed.2015.12.022

Cited by 62 publications

(68 citation statements)

References 59 publications

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“…The lipogenesis activation was associated to a different pattern of AGEs in the plasma and liver of sugar-drinking mice, with higher amount of glyoxal derived AGEs such, as glyoxal-lysine dimer (GOLD) and carboxymethyl lysine (CML), which are more resistant to AGEs-degrading enzymes, in the liver of the fructose group. The hypothesis that excessive intake of dietary sugars might interfere on lipid metabolism through the action of AGEs has been confirmed by the observation that the SREBP-activating protein SCAP is highly glycated by CML, a modification evoking prolonged activation of SCAP by inhibiting its degradation [12,36,56].…”

Section: Interference On Scap/srebp Lipogenic Pathwaymentioning

confidence: 97%

“…(SREBP-1c) and carbohydrate response element binding protein (ChREBP) [34][35][36]. A positive correlation between lipogenesis and plasma triglyceride has been described in patients with isocaloric feeding added with high fructose level [37].…”

Section: Lipogenic Effect Of Fructosementioning

confidence: 99%

“…In addition to the effects attributed to the excess of calories intake induced by high sugars consumption on metabolism, the sugar-derived AGEs have been shown in animal models to contribute to the development of pathological metabolic conditions through the interference on several protein functions and the activation of pro-inflammatory signals [36,40], as illustrated in the Scheme I below.…”

Section: Dietary Sugar-induced Glycation: Interference On Cell Functimentioning

confidence: 99%

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Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

Aragno¹,

Mastrocola²

2017

Preprint

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Abstract.The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beveragesconsumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health.Indeed, the here reviewed most recent reports on the effects of high sugars consumption and dietderived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

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Section: Interference On Scap/srebp Lipogenic Pathwaymentioning

confidence: 97%

Section: Lipogenic Effect Of Fructosementioning

confidence: 99%

Section: Dietary Sugar-induced Glycation: Interference On Cell Functimentioning

confidence: 99%

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Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

Aragno¹,

Mastrocola²

2017

Preprint

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“…Furthermore, in rats, dietary AGE exacerbate NAFLD via the generation of oxidative stress (122) . Their action could involve the stimulation of lipogenesis by SREBP-1c as suggested by Mastrocola et al (41,123) ; they showed in mice that fructose-induced CML accumulation could interact with the SREBP-cleavage activating protein (SCAP) leading to a prolonged activation of SREBP-1 (41) . The same phenomenon, also in mice, is observed in muscle and could participate in intramuscular fat deposition (123) .…”

Section: Secondary Diseasesmentioning

confidence: 99%

“…Their action could involve the stimulation of lipogenesis by SREBP-1c as suggested by Mastrocola et al (41,123) ; they showed in mice that fructose-induced CML accumulation could interact with the SREBP-cleavage activating protein (SCAP) leading to a prolonged activation of SREBP-1 (41) . The same phenomenon, also in mice, is observed in muscle and could participate in intramuscular fat deposition (123) . The relationship between HCIAS-induced insulin resistance and NAFLD has also been studied but this relationship is still poorly understood.…”

Section: Secondary Diseasesmentioning

confidence: 99%

Similarities and interactions between the ageing process and high chronic intake of added sugars

et al. 2017

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In our societies, the proportions of elderly people and of obese individuals are increasing. Both factors are associated with high health-related costs. During obesity, many authors suggest that it is a high chronic intake of added sugars (HCIAS) that triggers the shift towards pathology. However, the majority of studies were performed in young subjects and only a few were interested in the interaction with the ageing process. Our purpose was to discuss the metabolic effects of HCIAS, compare with the effects of ageing, and evaluate how deleterious the combined action of HCIAS and ageing could be. This effect of HCIAS seems mediated by fructose, targeting the liver first, which may lead to all subsequent metabolic alterations. The first basic alterations induced by fructose are increased oxidative stress, protein glycation, inflammation, dyslipidaemia and insulin resistance. These alterations are also present during the ageing process, and are closely related to each other, one leading to the other. These basic alterations are also involved in more complex syndromes, which are also favoured by HCIAS, and present during ageing. These include non-alcoholic fatty liver disease, hypertension, neurodegenerative diseases, sarcopenia and osteoporosis. Cumulative effects of ageing and HCIAS have been seldom tested and may not always be strictly additive. Data also suggest that some of the metabolic alterations that are more prevalent during ageing could be related more with nutritional habits than to intrinsic ageing. In conclusion, it is clear that HCIAS interacts with the ageing process, accelerates the accumulation of metabolic alterations, and that it should be avoided.

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Mangiferin modulation of metabolism and metabolic syndrome

Fomenko

Chi

2016

BioFactors

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The recent emergence of a worldwide epidemic of metabolic disorders, such as obesity and diabetes, demands effective strategy to develop nutraceuticals or pharmaceuticals to halt this trend. Natural products have long been and continue to be an attractive source of nutritional and pharmacological therapeutics. One such natural product is mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera indica L. Reports on biological and pharmacological effects of MGF increased exponentially in recent years. MGF has documented antioxidant and anti-inflammatory effects. Recent studies indicate that it modulates multiple biological processes involved in metabolism of carbohydrates and lipids. MGF has been shown to improve metabolic abnormalities and disorders in animal models and humans. This review focuses on the recently reported biological and pharmacological effects of MGF on metabolism and metabolic disorders.

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Fructose-derived advanced glycation end-products drive lipogenesis and skeletal muscle reprogramming via SREBP-1c dysregulation in mice

Cited by 62 publications

References 59 publications

Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

Similarities and interactions between the ageing process and high chronic intake of added sugars

Mangiferin modulation of metabolism and metabolic syndrome

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