Review: The metabolic syndrome as an endocrine disease: is there an effective pharmacotherapeutic strategy optimally targeting the pathogenesis?

Abstract

The metabolic syndrome (MetS) represents a combination of cardiovascular risk determinants such as obesity, insulin resistance and lipid abnormalities such as hypertriglyceridemia, increased free fatty acids, low high-density-cholesterol and hypertension. As a multiple component condition it imparts a doubling of relative risk for atherosclerotic cardiovascular disease (ASCVD). It is currently controversial which component of the syndrome carries what weight. There is even a considerable debate whether the risk for ASCVD is greater in patients diagnosed with MetS than that by the individual risk factors. At present, no unifying pathogenetic mechanism can explain the metabolic syndrome and there is no unique treatment for it. This review summarizes and critically reviews the currently available clinical and scientific evidence for the concept that the MetS is causally an endocrine disease and discusses pharmacotherapeutic strategies targeting the pathogenesis rather than single symptoms of the cluster.

Physical activity and cardiovascular performance – how important is cardiorespiratory fitness in childhood?

“…It has been well demonstrated that cardiometabolic risk factors frequently occur in obese youth and that these risk factors tend to cluster: obesity, insulin resistance, hypertension and lipid abnormalities (hypertriglyceridemia, increased free fatty acids, low HDL-cholesterol, increased LDL-cholesterol) are hypothesized to be the underlying mechanisms for this clustering of risk factors, known as the metabolic syndrome (MetS) (Schindler 2007). However, the number of studies examining the impact of physical activity on MetS in youth is limited.…”

The metabolic syndrome: common origins of a multifactorial disorder

“…In the USA, the prevalence of MetS is driven by the growing obesity “epidemic”, which is occurring throughout Western society and is particularly notable in south-eastern USA 14. In fact, MetS has reached epidemic proportions across the whole of the USA and, in unison, so has the expression of obesity, glucose intolerance, type 2 diabetes, vascular inflammation and a prothrombotic phenotype 6. It has been reported that the incidence of MetS increases with the severity of obesity and has been observed in 50% of obese adolescents 15.…”

“…Increased concentrations of visceral fat may be also contribute to an IR state, because, by its nature, it is more resistant to the metabolic effects of insulin than subcutaneous fat 6. Instead, it is more responsive to lipolytic hormones, glucocorticoids and catecholamines 53 54.…”

“…A criticism of MetS is its lack of weighting for the individual syndrome components, and consequently whether the syndrome as a whole counts more than the sum of its parts remains unclear 3. In addition, the proponents of MetS are often criticised for their failure to identify a unifying pathogenic mechanism5 or single genetic cause, which in turn has prevented the formulation of a unique treatment 6. It is likely that a seemingly simple mechanism has not been identified because MetS has a highly complex aetiology including inherited genes, intrauterine environment, abnormal patterns of fat accumulation and physical inactivity 7.…”

Lipoxygenase in Condition of Experimental Hypertriacylglycerolaemia

“…This activation induces the expression of the fatty acid transport protein and fatty acid translocase, which facilitates the transport of free fatty acids across the cell membrane. Activation of PPARα also directly increases the transcription of enzymes of the peroxisomal β-oxidation pathway and de novo fatty acid synthesis by blocking enzymes such as acetyl-CoA carboxylase and fatty acid synthase (Schindler, 2007). …”