Jennifer H Stern
- Assistant Professor, Medicine
- Assistant Professor, Physiology
- Assistant Professor, BIO5 Institute
- Member of the Graduate Faculty
After graduating college I served as a hospice counselor before pursuing a career in research. Working closely with terminally ill patients and their families sparked my interest in understanding the link between nutrition and the prevention of age-related diseases. Since this experience, I have been fortunate to train with experts in the fields of aging, metabolism, and obesity. Current Stern lab research aims to understand the role of glucoregulatory hormone signaling in the pathogenesis of obesity, type II diabetes mellitus, and aging. More than 25% of the U.S. population greater than 65 years old has Type II diabetes mellitus, representing the highest prevalence of diabetes of any age group. Most research aimed at understanding the consequences of obesity in aging have focused on insulin and downstream signaling cascades, overlooking a potential role for the hormone glucagon. Given that many prominent diabetes treatments target glucagon or glucagon signaling pathways, it is essential to understand the role of glucagon in aging. Our research examines 1) the role of glucagon signaling in obesity-accelerated aging, 3) the role of glucagon signaling in healthspan extension promoted by calorie restriction, and 4) the role of glucagon signaling in exercise mediated improvements in metabolic and physical function. This work will close a significant gap in our understanding of how glucagon alters aging, while allowing us to assess the potential risks associated with inhibition of glucagon signaling.
- Ph.D. Nutritional Biology
- University of California, Davis, Davis, California, United States
- M.S. Nutrition
- Arizona State University, Tempe, Arizona, United States
- B.S. Communication Studies
- Northwestern University, Evanston, Illinois, United States
Metabolism, Nutrition, and Diabetes
Aging and caloric restriction, Obesity and Type 2 Diabetes, sleep disturbance and metabolic dysfunction, Obesity related cancer development and progression
Honors ThesisMCB 498H (Fall 2021)
Independent StudyMCB 499 (Fall 2021)
Physiology SeriesPSIO 696A (Fall 2021)
Physiology Student ForumPS 696C (Fall 2021)
Topics in Metabolic DiseaseACBS 595B (Fall 2021)
ResearchPS 900 (Summer I 2021)
Directed ResearchECOL 392 (Spring 2021)
Directed ResearchMCB 792 (Spring 2021)
Directed RsrchMCB 392 (Spring 2021)
Honors ThesisPSIO 498H (Spring 2021)
Independent StudyPSIO 399 (Spring 2021)
Physiology SeriesPSIO 696A (Spring 2021)
Physiology Student ForumPS 696C (Spring 2021)
ResearchPS 900 (Spring 2021)
Rsrch Meth Psio SciPS 700 (Spring 2021)
ThesisPS 910 (Spring 2021)
Topics in Metabolic DiseaseACBS 595B (Spring 2021)
Directed ResearchMCB 792 (Fall 2020)
Honors Independent StudyPSIO 499H (Fall 2020)
Honors ThesisPSIO 498H (Fall 2020)
Independent StudyECOL 299 (Fall 2020)
Independent StudyPSIO 399 (Fall 2020)
Physiology SeriesPSIO 696A (Fall 2020)
Physiology Student ForumPS 696C (Fall 2020)
ResearchPS 900 (Fall 2020)
Rsrch Meth Psio SciPS 700 (Fall 2020)
Topics in Metabolic DiseaseACBS 595B (Fall 2020)
Honors Independent StudyPSIO 399H (Spring 2020)
Independent StudyPSIO 399 (Spring 2020)
ResearchPS 900 (Spring 2020)
ThesisCMM 910 (Spring 2020)
Rsrch Meth Psio SciPS 700 (Fall 2019)
- Beaudry, J. L., Kaur, K. D., Varin, E. M., Baggio, L. L., Cao, X., Mulvihill, E. E., Stern, J. H., Campbell, J. E., Scherer, P. E., & Drucker, D. J. (2019). The brown adipose tissue glucagon receptor is functional but not essential for control of energy homeostasis in mice. Molecular metabolism, 22, 37-48.More infoAdministration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the canonical GCGR is expressed in brown adipose tissue (BAT) the importance of BAT GCGR activity for the physiological control of body weight, or the response to GCG agonism, has not been defined.
- Stern, J. H., Arriaga, Y., Gupta, A., Verma, U., Karri, S., Syed, S., Khosama, L., Mansour, J., Meyer, J., Scherer, P. E., & Beg, M. S. (2019). Fasting and Glucose-Stimulated Changes in Plasma Glucagon in Pancreatic Cancer: Potential Biomarkers for Detection?. Pancreas, 48(1), e1-e3.
- Stern, J. H., Smith, G., Chen, S., Unger, R., Klein, S., & Scherer, P. E. (2019). Obesity dysregulates fasting-induced changes in glucagon secretion. The Journal of endocrinology.More infoHyperglucagonemia, a hallmark in obesity and insulin resistance promotes hepatic glucose output, exacerbating hyperglycemia and thus predisposing to the development type 2 diabetes. As such, glucagon signaling is a key target for new therapeutics to manage insulin resistance. We evaluated glucagon homeostasis in lean and obese mice and people. In lean mice, fasting for 24h caused a rise in glucagon. In contrast, a decrease in serum glucagon compared to baseline was observed in diet-induced obese mice between 8 and 24h of fasting. Fasting decreased serum insulin in both lean and obese mice. Accordingly, the glucagon:insulin ratio was unaffected by fasting in obese mice but increased in lean mice. Re-feeding (2h) restored hyperglucagonemia in obese mice. Pancreatic perfusion studies confirm that fasting (16h) decreases pancreatic glucagon secretion in obese mice. Consistent with our findings in the mouse, a mixed meal increased serum glucagon and insulin concentrations in obese humans, both of which decreased with time after a meal. Consequently, fasting and re-feeding less robustly affected glucagon:insulin ratios in obese compared to lean participants. The glucoregulatory disturbance in obesity may be driven by inappropriate regulation of glucagon by fasting and a static glucagon:insulin ratio.
- Nelson, M. D., Szczepaniak, L. S., Wei, J., Szczepaniak, E., Sánchez, F. J., Vilain, E., Stern, J. H., Bergman, R. N., Bairey Merz, C. N., & Clegg, D. J. (2016). Transwomen and the Metabolic Syndrome: Is Orchiectomy Protective?. Transgender health, 1(1), 165-171.More infoMale-to-female transsexual women or who undergo cross-sex hormone treatments experience increased health-related risks (e.g., increased rates of cardiovascular disease and premature death). Yet, the exact mechanism by which altering biochemistry leads to metabolic impairment remains unclear. While much attention has been paid to cross-sex hormone therapy, little is known about the metabolic risk associated with orchiectomy. To address the above limitation, we prospectively enrolled 12 transwomen: 4 who had undergone bi-lateral orchiectomy and 8 who had not. Both groups were using cross-sex hormones. Glucose tolerance was assessed using a standard 75g oral glucose tolerance test. Hepatic steatosis was assessed by H magnetic resonance spectroscopy. The amount of subcutaneous and visceral abdominal fat was determined from a single abdominal axial image at the level between the vertebral L2 and L3 bodies. Baseline venous fasting blood sampling was performed for measurement of hemoglobin A1c, glucose, insulin, sex hormones, and sex hormone binding globulin. The major novel findings were: (1) orchiectomy and cross-sex hormone therapy is associated with less hepatic steatosis and insulin resistance; (2) orchiectomy may be metabolically protective, and (3) circulating concentrations of sex hormones may be a major determinant of metabolic health in transwomen. To our knowledge, this is the first study to suggest an independent and protective role of orchiectomy on the metabolic health of transwomen.
- Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016). Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell metabolism, 23(5), 770-84.More infoMetabolism research has made tremendous progress over the last several decades in establishing the adipocyte as a central rheostat in the regulation of systemic nutrient and energy homeostasis. Operating at multiple levels of control, the adipocyte communicates with organ systems to adjust gene expression, glucoregulatory hormone exocytosis, enzymatic reactions, and nutrient flux to equilibrate the metabolic demands of a positive or negative energy balance. The identification of these mechanisms has great potential to identify novel targets for the treatment of diabetes and related metabolic disorders. Herein, we review the central role of the adipocyte in the maintenance of metabolic homeostasis, highlighting three critical mediators: adiponectin, leptin, and fatty acids.
- Rutkowski, J. M., Stern, J. H., & Scherer, P. E. (2015). The cell biology of fat expansion. The Journal of cell biology, 208(5), 501-12.More infoAdipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity.
- Stern, J. H., & Scherer, P. E. (2015). Adipose tissue biology in 2014: Advances in our understanding of adipose tissue homeostasis. Nature reviews. Endocrinology, 11(2), 71-2.
- Stern, J. H., Grant, A. S., Thomson, C. A., Tinker, L., Hale, L., Brennan, K. M., Woods, N. F., & Chen, Z. (2014). Short sleep duration is associated with decreased serum leptin, increased energy intake and decreased diet quality in postmenopausal women. Obesity (Silver Spring, Md.), 22(5), E55-61.More infoShort sleep duration induces hormonal perturbations contributing to hyperphagia, insulin resistance, and obesity. The majority of these studies are conducted in young adults. This analysis in a large (n = 769) sample of postmenopausal women (median age 63 years) sought to (a) confirm that sleep duration and sleep quality are negatively correlated with circulating leptin concentrations and (b) to examine the relationship between self-reported sleep, dietary energy intake, and diet quality, as well as, investigate the role of leptin in these associations.
- Stern, J. H., Kim, K., & Ramsey, J. J. (2014). The influence of shc proteins on the whole body energetic response to calorie restriction initiated in 3-month-old mice. ISRN nutrition, 2014, 562075.More infoThere is increasing evidence that Shc proteins play a role in energy metabolism, and we have previously reported that knockdown of Shc proteins influences the energetic response to acute (3 days) calorie restriction (CR) in 18-month-old mice. Whether Shc proteins play a role in the metabolic response to CR in younger mice has yet to be elucidated. Hence, we sought to determine the impact of 3 days and longer term (2 months) CR on energy expenditure (EE) and respiratory quotient (RQ) in 3 month-old Shc knockout (ShcKO) and wild-type (WT) mice. ShcKO mice decreased (P < 0.001) EE normalized for body weight (EEBW) by 3 days of CR, while no such change was observed in WT animals. However, both ShcKO and WT mice decreased (P < 0.001) EEBW at 2 months of CR and there were no differences in body weight between the ShcKO and WT mice at either 3 days or 2 months of CR. Consistent with increased fatty acid oxidation, only ShcKO mice maintained decreased (P < 0.001) 24 h RQ through 2 months of CR, suggesting that they were able to maintain increased fatty acid oxidation for a longer period of time than WT mice. These results indicate that Shc proteins may contribute to some of the acute energetic responses to CR.
- Stern, J. H., Kim, K., & Ramsey, J. J. (2012). The influence of acute, late-life calorie restriction on whole body energy metabolism in p66Shc(-/-) mice. Mechanisms of ageing and development, 133(6), 414-20.More infoIt has been proposed that Shc proteins may influence aging by regulating insulin signaling and energy metabolism. Evidence suggests that deletion of p66Shc could partially attenuate weight gain on a high fat diet by increasing energy expenditure. However, the impact of p66Shc on the metabolic response to calorie restriction (CR) has not been determined. Thus, we used indirect respiration calorimetry to determine the impact of CR on energy expenditure (EE) and substrate utilization (RQ) in 18mo p66Shc(-/-) and wild-type (WT) mice. Calorimetry measurements were completed at baseline and following 3d of 40% CR and 2 mo of 26% CR. There was no difference (P>0.10) in EE and RQ between gentoypes, regardless of how EE data was normalized. Both p66Shc(-/-) and WT mice showed decreases (P
- Stern, J. H., Kim, K., & Ramsey, J. J. (2012). The influence of shc proteins and aging on whole body energy expenditure and substrate utilization in mice. PloS one, 7(11), e48790.More infoWhile it has been proposed that Shc family of adaptor proteins may influence aging by regulating insulin signaling and energy metabolism, the overall impact of Shc proteins on whole body energy metabolism has yet to be elucidated. Thus, the purpose of this study was to determine the influence of Shc proteins and aging on whole body energy metabolism in a mouse model under ambient conditions (22°C) and acute cold exposure (12°C for 24 hours). Using indirect respiration calorimetry, we investigated the impact of Shc proteins and aging on EE and substrate utilization (RQ) in p66 Shc-/- (ShcKO) and wild-type (WT) mice. Calorimetry measurements were completed in 3, 15, and 27 mo mice at 22°C and 12°C. At both temperatures and when analyzed across all age groups, ShcKO mice demonstrated lower 24 h total EE values than that of WT mice when EE data was expressed as either kJ per mouse, or adjusted by body weight or crude organ mass (ORGAN) (P≤0.01 for all). The ShcKO mice also had higher (P
- Rossow, H. A., & Stern, J. H. (2011). Teaching comparative metabolism using a graphic computer model, Virtual Tissue. Advances in physiology education, 35(1), 99-102.
- Stern, J. H. (2020, January). Aberrant Glucagon Signaling in Obesity and a Potential Role in Aging. Endocrine Grand Rounds. University of Arizona College of Medicine, Division of Endocrinology: University of Arizona College of Medicine.
- Stern, J. H. (2019, April). Glucagon Signaling and the Adaptation to Exercise and Aging. Endocrine Works in Progress. University of Arizona College of Medicine, Division of Endocrinology: University of Arizona.
- Stern, J. H. (2019, April). Glucagon Signaling in the Metabolic Adaptation to Fasting and Obesity. University of Arizona Department of Physiology Seminar Series. University of Arizona Department of Physiology: University of Arizona.
- Stern, J. H. (2019, September). Aberrant Glucagon Signaling in Obesity and a Potential Role in Aging. School of Animal & Comparative Biomedical Sciences Seminar Series. University of Arizona School of Animal & Comparative Biomedical Sciences: University of Arizona.
- Stern, J. H., Vasileva, A., & Marx, T. (2019, October). Glucagon Signaling in Obesity and Aging. Third Annual Innovations and Inventions Research Showcase. University of Arizona, Tucson, AZ: University of Arizona.