An Interview with Tammy Kindel, MD, PhD, FACS, FASMBS
by Shaina R. Eckhouse, MD, FACS, FASMBS, and Omar M. Ghanem, MD, FACS
Dr. Ghanem is a bariatric surgeon at the Mayo Clinic in Rochester, Minnesota. Dr. Eckhouse is a bariatric surgeon at Washington University in St. Louis, Missouri.
Bariatric Times. 2023;20(2):24–25.
Dr. Tammy Kindel, an Associate Professor of Surgery at the Medical College of Wisconsin, received the 2016 American Society for Metabolic and Bariatric Surgery (ASMBS) research grant, funded by the ASMBS Foundation, for her study, titled “The effect of sleeve gastrectomy on obesity induced heart failure in rats.” The objective of this $25,000 grant focused on determining if a weight loss-independent effect exists in improving cardiac morphology and function following sleeve gastrectomy (SG). In this article, we highlight Dr. Kindel’s clinical and research career, and the clinical implications of her study. Additionally, we will explore the role that the ASMBS Foundation grant served in helping Dr. Kindel build an extramurally funded research career.
Dr. Kindel, can you please share your current clinical practice and research background as a surgeon scientist focusing on the hormonal and metabolic effects of bariatric surgery in the treatment of obesity?
Dr. Kindel: My research experience in the metabolic effects of bariatric surgery started in 2007. I took three years after my PGY2 year at Northwestern Memorial Hospital in Chicago to obtain a PhD in pathobiology and molecular medicine. My PhD thesis studied the role of a specific gut hormone, gastric inhibitory peptide (GIP), in the changes in glucose homeostasis after duodenal-jejunal exclusion. We used duodenal-jejunal exclusion as a surgical model to test the importance of duodenal exclusion from nutrient stimulation, found in both gastric bypass and biliopancreatic diversion, in terms of improved hyperglycemia. Following my PhD and completion of my residency, I underwent fellowship training at the University of Nebraska Omaha in Minimally Invasive and Bariatric Surgery. After my fellowship, I started as a faculty member in the Division of Minimally Invasive and Gastrointestinal Surgery at the Medical College of Wisconsin in Milwaukee. I started my basic and translational science lab interested in pivoting my prior work with gastrointestinal hormones from diabetes research to metabolic-associated cardiovascular disease. In 2018, I became the director of the bariatric surgeon program at Froedtert and the Medical College of Wisconsin, and I have a bariatric clinical practice with special interest in adolescent bariatric surgery, advanced heart failure, and complex revisional surgery.
You were awarded an ASMBS research grant in 2016, funded by the ASMBS Foundation. Could you further explain the aims of this grant?
Dr. Kindel: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that augments insulin secretion and improves glucose homeostasis, and it increases several-fold after SG. GLP-1 receptors are also present within the heart, and the clinical use of GLP-1 receptor agonists reduces ischemic burden after a myocardial infarction and improves cardiac function in patients with heart failure. In the research funded by our 2016 ASMBS research grant, we hypothesized that weight loss-independent increases in GLP-1 receptor signaling after SG improves cardiac structure and function in obesity-induced heart failure. To test this hypothesis, we developed two specific aims. The first aim was to determine if SG improves cardiac morphology and function in obesity-induced heart failure via a weight loss-independent mechanism, and the second aim was to determine if SG increases cardiac GLP-1 receptor signaling and function in obesity-induced heart failure via a weight loss-independent mechanism.
What were the results of your study?
Dr. Kindel: In our study, we induced obesity and cardiac dysfunction by feeding male, Wistar rats a high-fat diet. Rats underwent SG or sham surgery. Some rats that underwent sham surgery were pair-fed, meaning they were given the exact same daily amount of food consumed by SG rats. This allows us to test for weight loss-independent effects of surgery. If SG rats have a phenotype not seen in the weight-matched, pair-fed rats, then we assume that phenotype is unique to the gastrointestinal anatomy and weight loss-independent. We found that only the SG group had significant improvements in postoperative diastolic relaxation, as measured by isovolumetric relaxation time by echocardiography. SG significantly increased active GLP-1. SG also uniquely and significantly increased messenger ribonucleic acid (mRNA) cardiac gene expression of sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), a protein known to be downregulated in heart failure. This study was published in Surgery for Obesity and Related Diseases (SOARD), and we concluded that SG improves diastolic function, independent of weight loss, in a rat model of obesity, with beneficial alterations in cardiac gene expression of multiple known targets related to cardiac failure, including SERCA2a. These data support that a greater curve gastrectomy induces beneficial intracellular cardiac signaling for diastolic function mediated by the enterocardiac axis, possibly GLP-1 or bile acids, that is independent of weight loss and could translate to offering metabolic surgery to patients with heart failure with preserved ejection fraction.
Did the research grant funded by the ASMBS Foundation lead to further research projects? If so, could you share if you were able to utilize this initial grant funding as leverage for obtaining further funding for your research?
Dr. Kindel: Our initial study funded by the ASMBS research grant provided preliminary data to support KL2, K08, and Clowes American College of Surgeons career development awards. From these career development awards, we have learned that the gut microbiome and bile acid signaling are important mediators of the effect of SG on heart failure. Recently, I was awarded a $2.2 million, five-year R01 award from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) to further these mechanistic studies.
Do your studies support or refute that improvements of cardiac structure and function following bariatric surgery are weight loss-independent?
Dr. Kindel: We have found that, in multiple different rat strains of diet-induced obesity, rat models of genetic obesity, and mouse strains of diet-induced obesity, the beneficial effect of SG on diastolic function is persistent and convincing and supports a unique role of gastrectomy in weight loss-independent improvements in cardiac function and signaling.
One of the largest challenges with bench work is translating the findings to clinic medicine. How have the findings from the study funded by the ASMBS Foundation through the ASMBS research grant changed the management of patients with obesity and diastolic dysfunction?
Dr. Kindel: We are actively working on the translational aspects of these studies with our current R01 funding. An aim of this study is to collect biospecimens from patients with heart failure with preserved ejection fraction before and after SG to verify that the mechanisms involved in our animal models correctly translate to our human patients and support a robust improvement in diastolic function. My hope is that our work, and future work in conjunction with heart-failure related clinical trials, will support the utilization of metabolic surgery as treatment for obesity-associated heart failure with preserved ejection fraction beyond the weight loss and comorbidity improvement, similar to the direct indication for metabolic surgery as disease treatment for Type 2 diabetes mellitus.
Category: Past Articles, Research Grant Report
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