Two of the major factors predisposing to cardiovascular disease are diabetes mellitus and dyslipidemia. The Birnbaum lab tries to understand the normal pathways regulating hepatic lipid synthesis and secretion and how these processes are disrupted in insulin resistant states.
The Birnbaum Lab is researching the pathways that regulate hepatic lipid synthesis and secretion and the effect on these pathways of insulin resistance. Currently, the primary focus of the Lab's investigations include the regulation of de novo lipogenesis by the protein kinase Akt; control of lipoprotein secretory pathway by rapamycin complex 1 (mTORC1); and the role of AMP-activated protein kinase (AMPK) in lipid metabolism. Both Akt and AMPK are signaling molecules involved in the pathways that alert an organism to the absence of food and initiate an appropriate response. The mTORC1 complex, a downstream target positively regulated by Akt, is required in vivo for de novo lipogenesis and the expression of Srebp1c, a bHLH transcription factor that controls lipogenesis.
"Electron micrograph of a liver form a fed mouse showing active endoplasmic reticulum and glycogen granules.
MRI of wildtype and Akt1 null mouse on a high fat diet, showing protection from obesity in the absence of Akt1.
Fat accumulation in the liver of a mouse fed a high fat diet. The triglyceride droplets have been stained red.
The Birnbaum Lab is comprised of doctoral and post-doctoral researchers, research specialists and graduate students.
- Abby Shearin
- Bobby Monks
- Helen Chen
- Lisa DiPilato
- Cass Lutz
- Maureen Victoria
- Michelle Bland
- Moshe Bitterman
- Qingwei Chu
- Paul Titchnell
- Shlomit Koren
- Will Quinn
The Birnbaum Lab of the Penn Cardiovascular Institute publishes the findings of its clinical research in the nation's leading clinical journals.
- Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature. 2013 Feb 14;494(7436):256-60. PMID: 23292513
- Lazar MA, Birnbaum MJ. Physiology. De-meaning of metabolism. Science. 2012;336:1651-1652. PubMed PMID: 22745413.
- Lu M, Wan M, Leavens KF, Chu Q, Monks BR, Fernandez S, Ahima RS, Ueki K, Kahn CR, Birnbaum MJ. Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat Med. 2012;18:388-395. PubMed PMID: 22344295; PubMed Central PMCID: PMC3296881.
- Wan M, Easton RM, Gleason CE, Monks BR, Ueki K, Kahn CR, Birnbaum MJ. Loss of Akt1 in mice increases energy expenditure and protects against diet-induced obesity. Mol Cell Biol. 2012;32:96-106. PubMed PMID: 22037765; PubMed Central PMCID: PMC3255699.
- Wan M, Leavens KF, Saleh D, Easton RM, Guertin DA, Peterson TR, Kaestner KH, Sabatini DM, Birnbaum MJ. Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. Cell Metab. 2011;14:516-527. PubMed PMID: 21982711; PubMed Central PMCID: PMC3190164.
- Miller RA, Chu Q, Le Lay J, Scherer PE, Ahima RS, Kaestner KH, Foretz M, Viollet B, Birnbaum MJ. Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling. J Clin Invest. 2011;121:2518-2528. PubMed PMID: 21606593; PubMed Central PMCID: PMC3104763.
- Leavens KF, Birnbaum MJ. Insulin signaling to hepatic lipid metabolism in health and disease. Crit Rev Biochem Mol Biol. 2011;46:200-215. PubMed PMID: 21599535.