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

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, Chittaranjan S. Yajnik

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalCell metabolism
Issue number2
Early online date09 Jul 2015
Publication statusPublished - 04 Aug 2015


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