Our human constitutions are to a substantial degree, determined by genetics we inherit from our antecedents and the dietary habits of and foods available to one’s forbears have substantial influence on an individual’s healthy eating model today.
According to new research published this month in the journal Cell Metabolism, the burgeoning middle classes in and from developing countries are more susceptible than western Caucasians to obesity, type 2 diabetes and cardiovascular disease in today’s changing environment. An international team of scientists from the University of Sydney’s NHMRC Clinical Trials Centre in Sydney Australia, and the National Centre for Cell Science, KEM Hospital, the DYP Medical College the Indian Institute of Science Education and Research (IISER) , the National Toxicology Center — all at Pune, India, the Cardiovascular Institute, Mount Sinai School of Medicine, New York, the Department of Biostatistics at the University of Michigan, Ann Arbor, Michigan, and the Manipal Institute of Regenerative Medicine at Manipal University in Bangalore, India, have determined that this may be a result of the sort of nutrition upon which this demographic’s ancestors subsisted.
Findings detailed in the Cell Metabolism paper titled Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation (Cell Metabolism, 2015; DOI: 10.1016/j.cmet.2015.06.008), coauthored by Anandwardhan A. Hardikar, Sarang N. Satoor, Mahesh S. Karandikar, Mugdha V. Joglekar, Amrutesh S. Puranik, Wilson Wong, Sandeep Kumar, Amita Limaye, Dattatray S. Bhat, Andrzej S. Januszewski, Malati R. Umrani, Amaresh K. Ranjan, Kishori Apte, Pranav Yajnik, Ramesh R. Bhonde, Sanjeev Galande, Anthony C. Keech, Alicia J. Jenkins, and Chittaranjan S. Yajnik, could explain projections that by 2030 more than 70 percent of cases of type 2 diabetes globally will be suffered by individuals from developing countries.
The coauthors note that people in developing countries have faced multigenerational undernutrition, and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, although the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, the researchers demonstrate that undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. The scientists also found that undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and eight-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats.
And importantly, the research shows that these metabolic abnormalities are not reversed after two generations of unrestricted access to highly nutritious commercial chow (nutrient recuperation), the paper noting that altered epigenetic signatures in insulin-2 gene promoter region of undernourished rats are not reversed by nutrient recuperation. “Instead,” the coauthors observe, “this newly prosperous population favoured 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,” a genetic hangover to chronic undernutrition over many generations that may contribute to persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.
The scientists note that several previous studies have reported that a high-fat diet does obesity, observing that this latest research demonstrates that eating what has come to be regarded as ‘normal’ middle class diets can make susceptible animals obese if their ancestors had been undernourished for several generations.
A University of Sydney release notes that unsurprisingly, increasing economic prosperity in developing countries has been accompanied by a sudden increase in people’s caloric intake. However the epigenetic makeup of these populations whereby changing environmental factors that might be expected to alter how people’s genes are expressed, has not compensated for these rapid dietary changes. THe bodies of people living in or hailing from countries that have endured centuries of chronic undernutrition are still genetically “programmed” to anticipate and prepare for undernourishment; so they store fat in a manner that makes them more prone to obesity and its resulting diseases than are 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 and Australian Future Fellow (ARC) Anandwardhan A. Hardikar’s team at the University of Sydney in collaboration with research colleagues overseas. The first group of subject rats was undernourished for 50 generations, 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, and these rats were eight times more likely to develop diabetes and multiple metabolic defects when compared to the control group.
“Their adverse metabolic state was not reversed by two generations of nutrient recuperation through a normal diet,” says Associate Professor Hardikar. “Instead this newly prosperous population favoured 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.” Dr. Hardikar also notes that 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.”
Observing that with increasing migration of populations from developing to affluent countries, there is a need to identify factors that minimize their risk of diabetes and obesity, Associate Professor Hardikar says that “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.”
Associate Professor Hardikar is an Australian Future Fellow (ARC) and Group leader, Diabetes and Islet Biology at the NHMRC Clinical Trials Centre, University of Sydney.
Research at Dr. Hardikar’s lab is focused on understanding islet cell biology, specifically related to development, differentiation and death of human pancreatic beta cells. His team works with cadaveric human pancreatic islets as well as biliary duct and gallbladder-derived cells to gather information that would help them understand development of insulin-producing cells. Present research projects involve applying this information to differentiation of human pancreatic progenitor cells. In addition to these studies, other projects in the lab are focused on understanding the epigenetic modifications in insulin-producing cells in a unique model of multigeneration undernutrition. These studies involve understanding the influence of diet, micronutrients, intrautetine programming and gut microbiota in development of central adiposity, insulin resistance and type 2 diabetes.
Established in 1988, the University of Sydney’s NHMRC Clinical Trials Centre (CTC) now has a diverse group of 150 researchers, who have earned an outstanding reputation for contributing to major advances in clinical care via our high-quality collaborative clinical trials research.
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