Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

作者：Hardikar Anandwardhan A^*; Satoor Sarang N; Karandikar Mahesh S; Joglekar Mugdha V; Puranik Amrutesh S; Wong Wilson; Kumar Sandeep; Limaye Amita; Bhat Dattatray S; Januszewski Andrzej S; Umrani Malati R; Ranjan Amaresh K; Apte Kishori; Yajnik Pranav; Bhonde Ramesh R; Galande Sanjeev; Keech Anthony C; Jenkins Alicia J; Yajnik Chittaranjan S

来源：Cell Metabolism, 2015, 22(2): 312-319.

DOI：10.1016/j.cmet.2015.06.008

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.

• 出版日期2015-8-4