The type 2 diabetes susceptibility TCF7L2 gene variants affect postprandial glucose and fat utilization in non-diabetic subjects

Adamska, Edyta; Krętowski, Adam; Gościk, Joanna; Citko, Anna; Bauer, Witold; Waszczeniuk, Magdalena; Maliszewska, Katarzyna; Paczkowska-Abdulsalam, Magdalena; Niemira, Magdalena; Szczerbiński, Łukasz; Ciborowski, Michał; Górska, Maria

doi:10.1016/j.diabet.2017.05.001

Cited by 14 publications

(26 citation statements)

References 10 publications

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“…A population-based sample from the 1000PLUS cohort was enrolled in the present study, recruited between 2007-2017 as described previously [44][45][46]. The study is registered at ClinicalTrials.gov as NCT03792685.…”

Section: Study Populationmentioning

confidence: 99%

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Paczkowska-Abdulsalam

Niemira

Bielska

et al. 2020

IJMS

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Multiple mechanisms have been suggested to confer to the pathophysiology of metabolic syndrome (MetS), however despite great interest from the scientific community, the exact contribution of each of MetS risk factors still remains unclear. The present study aimed to investigate molecular signatures in peripheral blood of individuals affected by MetS and different degrees of obesity. Metabolic health of 1204 individuals from 1000PLUS cohort was assessed, and 32 subjects were recruited to four study groups: MetS lean, MetS obese, “healthy obese”, and healthy lean. Whole-blood transcriptome next generation sequencing with functional data analysis were carried out. MetS obese and MetS lean study participants showed the upregulation of genes involved in inflammation and coagulation processes: granulocyte adhesion and diapedesis (p < 0.0001, p = 0.0063), prothrombin activation pathway (p = 0.0032, p = 0.0091), coagulation system (p = 0.0010, p = 0.0155). The results for “healthy obese” indicate enrichment in molecules associated with protein synthesis (p < 0.0001), mitochondrial dysfunction (p < 0.0001), and oxidative phosphorylation (p < 0.0001). Our results suggest that MetS is related to the state of inflammation and vascular system changes independent of excess body weight. Furthermore, “healthy obese”, despite not fulfilling the criteria for MetS diagnosis, seems to display an intermediate state with a lower degree of metabolic abnormalities, before they proceed to a full blown MetS.

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Section: Study Populationmentioning

confidence: 99%

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Paczkowska-Abdulsalam

Niemira

Bielska

et al. 2020

IJMS

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“…In the randomly selected 47 healthy subjects the standardized meal tests were performed, accordingly to previously described procedures [11][12][13]34]. Taking into consideration the fact that investigated factors may be characterized by sexual dimorphism [35], only male participants were included in the study group.…”

Section: The Pre-and Post-meal Testsmentioning

confidence: 99%

“…Some of the SNPs may be associated with the weight gain due to larger amounts of consumed food, due to deprivation of postprandial satiety, as well as due to deprivation of energy expenditure and/or substrate utilization [5][6][7][8][9][10]. In our previous studies, we have noticed that some of the metabolic changes may appear only in postprandial state, and that postprandial metabolism can be dependent on the meal content [11,12], as well as on the carried genetic variants [13,14]. It is beyond any doubts that genetic factors predispose to obesity, however, obesity should not be considered only as a genetic disorder.…”

Section: Introductionmentioning

confidence: 99%

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans

et al. 2019

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PurposeThe interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization.MethodsWe genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake.ResultsWe found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024).ConclusionsWe have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.

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“…The study was conducted among Caucasian men of Polish origin, who were recruited to the meal test studies for our other experiments [ 14 , 15 , 16 ]. Therefore, study population, study procedures, and statistical analysis have been described in detail previously.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Energy Expenditure and Oxidation of Energy Substrates in Adult Males after Intake of Meals with Varying Fat and Carbohydrate Content

et al. 2018

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Obesity is a result of positive energy balance. The aim of this study was to measure (in crossover trials) the energy expenditure and oxidation of glucose and lipids, both at the fasting state and after an intake of meals with a varying macronutrient content, in normal-weight and overweight/obese people. In the study, 46 healthy adult males (23 with normal body weight and 23 overweight/obese), aged 21–58, were examined. During two consecutive visits, subjects received isocaloric standardized meals (450 kcal) with different content of basic nutrients. Resting metabolic rate and carbohydrate and fat utilization were evaluated during the fasting state and postprandially, using an indirect calorimetry method. Energy expenditure was higher in people with normal body weight and slightly higher after the high-carbohydrate meal. In overweight/obese people, increased expenditure was noted after normo-carbohydrate meal intake. The high-fat meal induced lower postprandial thermal response compared to a high-carbohydrate meal, both in people with normal body weight and in overweight/obese men. Glucose utilization was higher after the high-carbohydrate meal, and it was higher in the normal body weight group than in overweight/obese people. In addition, overweight/obese people showed a lower level of fatty acid oxidation under fasting conditions which, together with limited ability to oxidize energy substrates, depending on their availability, indicates that these people are characterized by lower metabolic flexibility.

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The type 2 diabetes susceptibility TCF7L2 gene variants affect postprandial glucose and fat utilization in non-diabetic subjects

Cited by 14 publications

References 10 publications

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans

Evaluation of Energy Expenditure and Oxidation of Energy Substrates in Adult Males after Intake of Meals with Varying Fat and Carbohydrate Content

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