TY - JOUR
T1 - Allograft inflammatory factor-1-like is a situational regulator of leptin levels, hyperphagia, and obesity
AU - Parikh, Dippal
AU - Jayakumar, Smitha
AU - Oliveira-Paula, Gustavo H.
AU - Almonte, Vanessa
AU - Riascos-Bernal, Dario F.
AU - Sibinga, Nicholas E.S.
N1 - Funding Information:
Supported by NIH R01HL128066, R21NS16480, and R21AI171739 (N.E.S.S.), F31HL144041 and T32 GM007491 (V.A.), American Heart Association 20TPA35490392 (N.E.S.S.) and Career Development Award 19CDA34660217 (D.F.R-B.). We would like to thank Cergentis BV (Utrecht, the Netherlands) for performing the TLA and sequencing. We would like to thank Gary Schwartz (Einstein) for key advice and the Einstein Diabetes Center Animal Physiology core facility for assistance with performing Echo-MRI, CT scans, and metabolic cage studies. We would also like to thank the histopathology core facility and biomarker analytic research core (BARC) Einstein for help with H&E staining and serum analyte measurements, respectively. We would also like to acknowledge that the graphical abstract was created with biorender.com. Conception and design N.E.S.S. D.P.; Performance of experiments D.P. D.F.R-B. S.J. G.O-P. V.A.; Analysis of data D.P. D.F.R-B. N.E.S.S.; Figures and writing D.P. N.E.S.S. The author(s) declare no competing interests.
Funding Information:
Supported by NIH R01HL128066 , R21NS16480 , and R21AI171739 (N.E.S.S.), F31HL144041 and T32 GM007491 (V.A.), American Heart Association 20TPA35490392 (N.E.S.S.) and Career Development Award 19CDA34660217 (D.F.R-B.). We would like to thank Cergentis BV (Utrecht, the Netherlands) for performing the TLA and sequencing. We would like to thank Gary Schwartz (Einstein) for key advice and the Einstein Diabetes Center Animal Physiology core facility for assistance with performing Echo-MRI, CT scans, and metabolic cage studies. We would also like to thank the histopathology core facility and biomarker analytic research core (BARC) Einstein for help with H&E staining and serum analyte measurements, respectively. We would also like to acknowledge that the graphical abstract was created with biorender.com .
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10/21
Y1 - 2022/10/21
N2 - Mouse models enable the study of genetic factors affecting the complex pathophysiology of metabolic disorders. Here, we identify reductions in leptin levels, food intake, and obesity due to high-fat diet, accompanied by increased leptin sensitivity, in mice that harbor the E2a-Cre transgene within Obrq2, an obesity quantitative trait locus (QTL) that includes the leptin gene. Interestingly, loss of allograft inflammatory factor-1-like (AIF1L) protein in these transgenic mice leads to similar leptin sensitivity, yet marked reversal of the obesity phenotype, with accelerated weight gain and increased food intake. Transgenic mice lacking AIF1L also have low circulating leptin, which suggests that benefits of enhanced leptin sensitivity are lost with further impairment of leptin expression due to loss of AIF1L. Together, our results identify AIF1L as a genetic modifier of Obrq2 and leptin that affects leptin levels, food intake, and obesity during the metabolic stress imposed by HFD.
AB - Mouse models enable the study of genetic factors affecting the complex pathophysiology of metabolic disorders. Here, we identify reductions in leptin levels, food intake, and obesity due to high-fat diet, accompanied by increased leptin sensitivity, in mice that harbor the E2a-Cre transgene within Obrq2, an obesity quantitative trait locus (QTL) that includes the leptin gene. Interestingly, loss of allograft inflammatory factor-1-like (AIF1L) protein in these transgenic mice leads to similar leptin sensitivity, yet marked reversal of the obesity phenotype, with accelerated weight gain and increased food intake. Transgenic mice lacking AIF1L also have low circulating leptin, which suggests that benefits of enhanced leptin sensitivity are lost with further impairment of leptin expression due to loss of AIF1L. Together, our results identify AIF1L as a genetic modifier of Obrq2 and leptin that affects leptin levels, food intake, and obesity during the metabolic stress imposed by HFD.
KW - Endocrine system physiology
KW - Molecular physiology
KW - Obesity medicine
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U2 - 10.1016/j.isci.2022.105058
DO - 10.1016/j.isci.2022.105058
M3 - Article
AN - SCOPUS:85138772474
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 10
M1 - 105058
ER -
