title: p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.
abstract: BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity.
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Litwak
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Stanley
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Evan G
authors.initials: EG
authors.lastname: Pappas
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Jibran A
authors.initials: JA
authors.lastname: Wali
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Selck
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Melbourne, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
authors.affiliation: St Vincent's Institute of Medical Research, Melbourne, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Esteban N
authors.initials: EN
authors.lastname: Gurzov
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D007328:Insulin; D020738:Leptin; C488588:PUMA protein, mouse; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D005947:Glucose