The metabolic syndrome: the crossroads of diet and genetics

Abstract

The metabolic syndrome is a very common disease associated with an increased risk of type 2 diabetes mellitus (T2DM) and CVD. The clinical characteristics of the metabolic syndrome include insulin resistance, dyslipidaemia, abdominal obesity and hypertension. The diverse clinical characteristics illustrate the complexity of the disease process, which involves several dysregulated metabolic pathways. Thus, multiple genetic targets must be involved in the pathogenesis and progression of the metabolic syndrome. Nevertheless, the human genome has not changed markedly in the last decade but the prevalence of the metabolic syndrome has increased exponentially, which illustrates the importance of gene–environmental interactions. There is good evidence that nutrition plays an important role in the development and progression of the metabolic syndrome. Indeed, obesity is a key aetiological factor in the development of the metabolic syndrome. Understanding the biological impact of gene–nutrient interactions will provide a key insight into the pathogenesis and progression of diet-related polygenic disorders, including the metabolic syndrome. The present paper will explore the interactions between genetic background and dietary exposure or nutritional therapy, focusing on the role of dietary fatty acids within the context of nutrient regulation of gene expression and individual responsiveness to dietary therapy. Only with a full understanding of gene–gene, gene–nutrient and gene–nutrient–environment interactions can the molecular basis of the metabolic syndrome be solved to minimise the adverse health effects of obesity and reduce the risk of the metabolic syndrome, and subsequent T2DM and CVD.

Prevalence of Metabolic Syndrome in Japanese-Brazilians According to Specific Definitions for Ethnicity

“…Obesity, a key etiological factor for metabolic syndrome development, is directly infl uenced by nutritional habits. 16 As shown by Freire et al 17 and Sartorelli et al, 18 the current dietary pattern of Japanese-Brazilians contrasts with the traditional Japanese diet, particularly concerning the higher proportion of fat and refi ned grains intake and very high consumption of fruits and fruit juices.…”

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

“…The metabolic syndrome or insulin resistance syndrome is characterised by clustering of a group of symptoms related to insulin resistance, impaired glucose tolerance or diabetes, obesity, hypertension and dyslipidaemia (raised triacylglycerol [TAG] level and low HDL) [1][2][3]. The clustering of these symptoms has been suggested to be a better predictor of type 2 diabetes [4] and cardiovascular disease [5,6] than expected from the individual components.…”

“…Multivariate . Obesity Abbreviations A additive genetic variance a 2 the proportion of phenotypic variance explained by additive genetic effects AIR acute insulin response BIGTT OGTT-derived index C common environmental variance shared by a twin pair c 2 the proportion of phenotypic variance explained by common environmental effects D dominance genetic variance DZ dizygote E environmental variance specific to individuals e 2 the proportion of phenotypic variance explained by specific individual environmental effects HOMA homeostasis model assessment…”

Complexity of type 2 diabetes mellitus data sets emerging from nutrigenomic research: A case for dimensionality reduction?

“…Lack of replication may be attributed to small effect size, population stratification and/or too few study participants (rev. in [70,71]). Well-designed and highly-powered studies are needed to unravel the complexity of gene-nutrient interactions underlying T2DM and its precursor, the metabolic syndrome.…”