TY - JOUR
T1 - Multigenerational undernutrition increases susceptibility to obesity and diabetes that is not reversed after dietary recuperation
AU - Hardikar, Anandwardhan A.
AU - Satoor, Sarang N.
AU - Karandikar, Mahesh S.
AU - Joglekar, Mugdha V.
AU - Puranik, Amrutesh S.
AU - Wong, Wilson
AU - Kumar, Sandeep
AU - Limaye, Amita
AU - Bhat, Dattatray S.
AU - Januszewski, Andrzej S.
AU - Umrani, Malati R.
AU - Ranjan, Amaresh K.
AU - Apte, Kishori
AU - Yajnik, Pranav
AU - Bhonde, Ramesh R.
AU - Galande, Sanjeev
AU - Keech, Anthony C.
AU - Jenkins, Alicia J.
AU - Yajnik, Chittaranjan S.
PY - 2015
Y1 - 2015
N2 - People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show 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. Undernourished rats also have 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. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.
AB - People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show 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. Undernourished rats also have 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. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.
UR - https://hdl.handle.net/1959.7/uws:59244
U2 - 10.1016/j.cmet.2015.06.008
DO - 10.1016/j.cmet.2015.06.008
M3 - Article
SN - 1550-4131
VL - 22
SP - 312
EP - 319
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -