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 journalArticle

39 Citations (Scopus)

Abstract

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
Volume22
Issue number2
Early online date09 Jul 2015
DOIs
Publication statusPublished - 04 Aug 2015

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Malnutrition
Obesity
Insulin
Food
Glucose Clamp Technique
Experimental Diabetes Mellitus
Metabolome
Adiponectin
Metabolic Diseases
Adiposity
Low Birth Weight Infant
Homocysteine
Vitamin B 12
Leptin
Folic Acid
Genetic Promoter Regions
Epigenomics
Endotoxins
Developing Countries
Insulin Resistance

Cite this

Hardikar, A. A., Satoor, S. N., Karandikar, M. S., Joglekar, M. V., Puranik, A. S., Wong, W., ... Yajnik, C. S. (2015). Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation. Cell metabolism, 22(2), 312-319. https://doi.org/10.1016/j.cmet.2015.06.008
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. / Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation. In: Cell metabolism. 2015 ; Vol. 22, No. 2. pp. 312-319.
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Hardikar, AA, Satoor, SN, Karandikar, MS, Joglekar, MV, Puranik, AS, Wong, W, Kumar, S, Limaye, A, Bhat, DS, Januszewski, AS, Umrani, MR, Ranjan, AK, Apte, K, Yajnik, P, Bhonde, RR, Galande, S, Keech, AC, Jenkins, AJ & Yajnik, CS 2015, 'Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation', Cell metabolism, vol. 22, no. 2, pp. 312-319. https://doi.org/10.1016/j.cmet.2015.06.008

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

In: Cell metabolism, Vol. 22, No. 2, 04.08.2015, p. 312-319.

Research output: Contribution to journalArticle

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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.

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