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

doi:10.1016/j.cmet.2015.06.008

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

Research output: Contribution to journal › Article › peer-review

78 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 language	English
Pages (from-to)	312-319
Number of pages	8
Journal	Cell Metabolism
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2015.06.008
Publication status	Published - 2015

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SDG 3 Good Health and Well-being

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10.1016/j.cmet.2015.06.008

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Hardikar, A. A., Satoor, S. N., Karandikar, M. S., Joglekar, M. V., Puranik, A. S., Wong, W., Kumar, S., Limaye, A., Bhat, D. S., Januszewski, A. S., Umrani, M. R., Ranjan, A. K., Apte, K., Yajnik, P., Bhonde, R. R., Galande, S., Keech, A. C., Jenkins, A. J., & 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

@article{8ddc18f641f84189be7da27a94414a90,

title = "Multigenerational undernutrition increases susceptibility to obesity and diabetes that is not reversed after dietary recuperation",

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.",

author = "Hardikar, \{Anandwardhan A.\} and Satoor, \{Sarang N.\} and Karandikar, \{Mahesh S.\} and Joglekar, \{Mugdha V.\} and Puranik, \{Amrutesh S.\} and Wilson Wong and Sandeep Kumar and Amita Limaye and Bhat, \{Dattatray S.\} and Januszewski, \{Andrzej S.\} and Umrani, \{Malati R.\} and Ranjan, \{Amaresh K.\} and Kishori Apte and Pranav Yajnik and Bhonde, \{Ramesh R.\} and Sanjeev Galande and Keech, \{Anthony C.\} and Jenkins, \{Alicia J.\} and Yajnik, \{Chittaranjan S.\}",

year = "2015",

doi = "10.1016/j.cmet.2015.06.008",

language = "English",

volume = "22",

pages = "312--319",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "2",

}

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

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

C2 - 26166746

SN - 1550-4131

VL - 22

SP - 312

EP - 319

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

Multigenerational undernutrition increases susceptibility to obesity and diabetes that is not reversed after dietary recuperation

Abstract

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