Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood

Francisco, Flávio Andrade; Barella, Luiz F.; Silveira, Sandra da Silva; Saavedra, Lucas Paulo Jacinto; Prates, Kelly Valério; Alves, Vander Silva; Franco, Claudinéia Conationi da Silva; Miranda, Rosiane Aparecida; Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Malta, Ananda; Vieira, Elaine; Palma‐Rigo, Kesia; Pavanello, Audrei; Martins, Isabela Peixoto; Moreira, Veridiana Mota; Oliveira, Júlio Cézar de; Mathias, Paulo Cézar de Freitas; Gomes, Rodrigo Mello

doi:10.1007/s00394-016-1330-x

Cited by 24 publications

(24 citation statements)

References 39 publications

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“…87 In a study by Francisco et al, the oral administration of MG to breastfeeding rats conducted to increased milk glycotoxins content and impaired lipid profile and β-cell function, and more adiposity in the offspring. 88 Infant formulas are typically rich in sugars and proteins, and their industrial production includes heat exposition, increasing their AGEs, such as (carboxymethyl)lysine (CML), for almost 35-fold higher than in the breastmilk of healthy mothers. 89,90 Their absorption was confirmed in previous studies demonstrating a correlation between formula AGEs and their circulating levels and excretion in newborns.…”

Section: Early Exposure To Glycotoxins and Metabolic Impairment In Adult Lifementioning

confidence: 99%

“…In animal models, increased glycotoxin levels were observed in cows' milk maintained with a high AGEs diet 87 . In a study by Francisco et al , the oral administration of MG to breastfeeding rats conducted to increased milk glycotoxins content and impaired lipid profile and β‐cell function, and more adiposity in the offspring 88 …”

Section: Mechanism Of Metabolic Disease Programmingmentioning

confidence: 99%

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Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

Grilo

Tocantins

Diniz

et al. 2021

Eur J Clin Investigation

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Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non-communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non-communicable chronic diseases are associated with earlylife adaptations that produce long-term dysfunction. Early-life environment sets the long-term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling-related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or 2 of 21 | GRILO et aL.

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Section: Early Exposure To Glycotoxins and Metabolic Impairment In Adult Lifementioning

confidence: 99%

Section: Mechanism Of Metabolic Disease Programmingmentioning

confidence: 99%

Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

Grilo

Tocantins

Diniz

et al. 2021

Eur J Clin Investigation

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“…The maternal exposure to MGO (60 mg/kg/day by gavage) during the lactation period is able to negatively affect the rat offspring leading to T2D later in life, possibly by changes in breast milk composition. In detail, male offspring at 90 days of life show glucose intolerance, failure in β-cell function, increased body weight and dyslipidemia [106].…”

Section: Dicarbonyl Stress In Aging-related Diseasesmentioning

confidence: 99%

Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging

Nigro

Leone

Fiory

et al. 2019

Cells

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Dicarbonyl stress occurs when dicarbonyl metabolites (i.e., methylglyoxal, glyoxal and 3-deoxyglucosone) accumulate as a consequence of their increased production and/or decreased detoxification. This toxic condition has been associated with metabolic and age-related diseases, both of which are characterized by a pro-inflammatory and pro-oxidant state. Methylglyoxal (MGO) is the most reactive dicarbonyl and the one with the highest endogenous flux. It is the precursor of the major quantitative advanced glycated products (AGEs) in physiological systems, arginine-derived hydroimidazolones, which accumulate in aging and dysfunctional tissues. The aging process is characterized by a decline in the functional properties of cells, tissues and whole organs, starting from the perturbation of crucial cellular processes, including mitochondrial function, proteostasis and stress-scavenging systems. Increasing studies are corroborating the causal relationship between MGO-derived AGEs and age-related tissue dysfunction, unveiling a previously underestimated role of dicarbonyl stress in determining healthy or unhealthy aging. This review summarizes the latest evidence supporting a causal role of dicarbonyl stress in age-related diseases, including diabetes mellitus, cardiovascular disease and neurodegeneration.

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“…Hence, the lower serum FA concentrations in the subclinically ketotic cows compared with non-subclinically ketotic cows in the present study confirm the hypoglycemic state of these cows. In humans, MGO is commonly considered a marker of glycation that goes along with increased serum FA (Adeshara and Tupe, 2016), whereas in rats MGO has been shown to be correlated with milk FA (Francisco et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Methylglyoxal: A newly detected and potentially harmful metabolite in the blood of ketotic dairy cows

Dai

et al. 2018

Journal of Dairy Science

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Ketosis causes serious economic losses for the modern dairy industry because it is a highly prevalent metabolic disease among cows in high-producing herds during the transition period. Due to some striking similarities between diabetes in humans and ketosis in dairy cows, there is potential for the use of methylglyoxal (MGO)-commonly used in human diabetics-as a biomarker in dairy cattle. However, currently no data are available about the presence of MGO in the serum of dairy cattle or about the characteristics of its production or its potential contribution in the pathogenesis of ketosis. To determine the potential origin and pathway of formation of MGO, cows in different metabolic conditions [i.e., non-subclinically ketotic dairy cows in early lactation (n = 7), subclinically ketotic dairy cows in early lactation (n = 8), overconditioned dry cows (BCS >4.25, n = 6), and nonlactating heifers (n = 6)] were selected. Serum MGO concentrations were determined and correlated with indicators of the glucose and lipid metabolism and with haptoglobin (Hp) as an inflammatory marker. The serum MGO concentrations in subclinically ketotic cows (712.60 ± 278.77 nmol/L) were significantly greater than in nonlactating heifers (113.35 ± 38.90 nmol/L), overconditioned dry cows (259.71 ± 117.97 nmol/L), and non-subclinically ketotic cows (347.83 ± 63.56 nmol/L). In serum of lactating cows, concentrations of glucose and fructosamine were lower than in heifers and were negatively correlated with MGO concentrations. Even so, concentrations of metabolic and inflammatory markers such as dihydroxyacetone phosphate, nonesterified fatty acids, β-hydroxybutyrate, acetone, and Hp were remarkably higher in subclinically ketotic cows compared with nonlactating heifers; these metabolites were also positively correlated with MGO. In human diabetics elevated MGO concentrations are stated to originate from both hyperglycemia and the enhanced lipid metabolism, whereas higher MGO concentrations in subclinically ketotic cows were not associated with hyperglycemia. Therefore, our data suggest MGO in dairy cows to be a metabolite produced from the metabolization of acetone within the lipid metabolization pathway and from the metabolization of dihydroxyacetone phosphate. Furthermore, the highly positive correlation between MGO and Hp suggests that this reactive compound might be involved in the proinflammatory state of subclinical ketosis in dairy cows. However, more research is needed to determine the potential use of MGO as a biomarker for metabolic failure in dairy cows.

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Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood

Abstract: Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.

Cited by 24 publications

References 39 publications

Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging

Methylglyoxal: A newly detected and potentially harmful metabolite in the blood of ketotic dairy cows

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