Obese but healthy, thin but suffering from a multitude of disorders including metabolic syndrome. For years, this clinical observation, also known as metabolic healthy obese, has befuddled doctors and medical researchers, and motivated significant amount of research aimed at understanding the aetiology of obesity and its implications in health and disease.
Why would obesity be associated with health, while a thin physique may be hiding dangerous clinical symptoms of heart disease and diabetes? One hypothesis posits that if excess lipids are capable of being removed from the bloodstream and deposited into a fat layer around the organs, risks of developing major illnesses of the cardiovascular system such as atherosclerosis and heart attack are lower compared to those unable to remove excess lipids from blood.
By performing gene sequencing of two cohorts of people: one comprising healthy obese persons while the other a group of thin but unhealthy people, a study described in Guardian, Link identified three genes involved in lipid metabolism that may underlie the aetiology of heart disease as well as metabolic syndrome. Specifically, the genetic basis identified came through comprehensive analysis of fat tissue of subjects and co-expression analysis linking genes to clinical phenotype.
However, while the study (PLoS ONE, Link) identified genes implicated in lipid transport that may potentiate serious diseases of the heart and sugar metabolism, the role of other factors such as environment on the function of these genes remains unclear. Specifically, given the possibility of environmental factors modulating the expression of genes through a process known as epigenetics, the interplay of genes and environment is likely to be more complex than current clinical observations suggest.
More importantly, roles of these genes in the compendium of signaling and metabolic pathways would need to be further studied to understand, holistically, the relative importance of metabolism and signaling as well as immunology in mediating early onset disease states of diabetes and heart disease.
Thus, identification of three genes known to be involved in lipid transport and metabolism provide the necessary basis for further work in elucidating the signaling cascade, metabolic choke points and immunological disturbance thought to be important in the events leading to development of full blown metabolic syndrome and heart disease. Roles of immune cells in metabolic syndrome and diabetes have been documented but their possible link to genes involved in lipid metabolism remain tenuous. Specifically, immune genes such as interleukin 6 and interleukin 1B found to be highly differentially co-expressed with disease genes highlight the immunological aspect of disturbed lipid metabolism. Collectively, knowledge of genes involved in a pathway implicated in disease provide the incision point for more research unveiling finer and more granular details of the disease mechanisms, which along the way, highlights points for drug development and clinical treatment.
Category: biochemistry, metabolism, cell biology, molecular biology, health, genetics, genomics,
Tags: diabetes, metabolic syndrome, lipid metabolism, genome sequencing, co-expression analysis, fat tissue, obesity,