In a 12-year study with over 50 generations, rats who had undernourished ancestors were found to be more susceptible to diabetes and other metabolic diseases…
The middle classes from developing countries are more susceptible than western Caucasians to obesity, type 2 diabetes and cardiovascular disease in today’s changing environment. New research published today in Cell Metabolism from the University of Sydney’s NHMRC Clinical Trials Centre, the National Centre for Cell Science, KEM Hospital and the DYP Medical College, Pune, India reveals this may be a result of the nutrition endured by their ancestors.
The findings in the new paper could explain projections that more than 70 per cent of the global burden of type 2 diabetes will fall on individuals from developing countries by 2030.
Several studies have reported that a high-fat diet causes obesity. This latest research demonstrates that even eating a ‘normal’ diet can make animals obese, if their ancestors had been undernourished for several generations.
Unsurprisingly, increasing prosperity in developing countries has been accompanied by a sudden increase in caloric intake. However their populations’ epigenetic makeup, whereby changing environmental factors alter how people’s genes are expressed, has not compensated for these dietary changes. This means their bodies are still designed to cope with undernourishment; so they store fat in a manner that makes them more prone to obesity and its resulting diseases than populations accustomed to several generations of a ‘normal’ diet.
This scenario was recreated in a 12-year study of two groups of rats by Associate Professor Anandwardhan A. Hardikar’s team at the University of Sydney with colleagues overseas. The first group was undernourished for 50 generations and then put on a normal diet for two generations. The second (control) group maintained a normal diet for 52 generations. At the end of the study it was found that when the descendants of the first group were exposed to a normal diet, this did not reverse the epigenetic modifications made by their undernourished forebears. These rats were eight times more likely to develop diabetes and multiple metabolic defects when compared to the control group.
The undernourished rats exhibited low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also had higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats.
“Their adverse metabolic state was not reversed by two generations of nutrient recuperation through a normal diet,” said Associate Professor Hardikar. “Instead this newly prosperous population favored storage of the excess nutrients as fat leading to increased obesity, cardiovascular disease and metabolic risk for diabetes when compared to their ‘developed world’ counterparts.”
Associate Professor Hardikar said lower Vitamin B12 levels in the undernourished rats could also be an indicator of this trend. “Human studies from Ranjan Yajnik’s group at KEM Hospital in Pune, India have demonstrated that low circulating B12 and high folate levels are associated with insulin resistance and type 2 diabetes.” “Hopefully further research in understanding their gut microbes, which are major producers of Vitamin B12 in our body, and/or dietary supplementation with Vitamin B12 and other micronutrients, could reduce the risk of metabolic diseases in the coming generations.”
University of Sydney News Release. Anandwardhan A. Hardikar. Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation. Cell Metabolism. Available online 9 July 2015. doi:10.1016/j.cmet.2015.06.008.