Kevin L. Grove
Obesity is among the most common health risks facing young children today. A disturbing 17% of children are obese (in the 95th percentile for their weight). Obesity greatly impacts the quality of life that children will lead and will put them at nearly quadruple the risk of getting other life threatening diseases later in life, including diabetes, cardiovascular disease, and cancer. Furthermore, several early-onset metal disorders that have had a disturbing rise over the past couple of decades are also associated with poor maternal health and diet, including Anxiety/Depression, Attention Deficit/Hyperactivity Disorder (ADHD), and even Autism. It is estimated that the annual health care costs associated with adult obesity exceed $250 billion; however, the costs of treating the complications of obesity starting in childhood are immeasurable. Calculating the true impact on the quality of life is impossible. Our mandate is to improve the long-term health and well-being of children by understanding how maternal health and nutrition impact fetal and infant development. It is our belief that improving maternal health and nutrition prior to or during pregnancy can dramatically improve neonatal health, and reduce or even prevent chronic disease in offspring. By providing the specific tools and knowledge of the positive benefit that these simple lifestyle changes can make during this vulnerable period of development, the health and quality of life for both mother and baby can be improved. This, in turn, can provide positive benefits for the community and society as a whole.
The Grove laboratory has several main areas of research focus, all of which have a general theme around the regulation of energy homeostasis. A major focus of our group is the investigation of the progression of metabolic disease, as well as therapeutic interventions. All of the studies in our group involve both rodents (rat and mouse) and nonhuman primates (NHP).
- We are interested in the development of metabolic systems. More specifically, we are interested in the impact of maternal health and diet and postnatal nutrition on the development of these systems and the long-term impact on metabolic health. The primary focus of these studies is the development of hypothalamic neurocircuitry that controls food intake and sympathetic outflow. Some of the key findings of these studies are that the chronic consumption of a diet high in fat during pregnancy causes fetal lipotoxicity, resulting in oxidative damage and activation of inflammatory cytokines in the fetal liver, pancreas, and hypothalamus. The damage to these systems during the critical period of development predisposes the offspring to numerous metabolic diseases later in life, including obesity, diabetes, and cardiovascular disease.
- We are interested in the progression of metabolic disease induced by a high fat diet. These studies primarily use adult rhesus macaques consuming a high fat diet (HFD, 35% calories from fat diet). Similar to humans, these animals become obese, insulin resistant, develop hypertension, atherosclerosis, and eventually diabetes. A main focus of these studies is to determine the role of hyperlipidemia and proinflammatory cytokines in the development of the cardiovascular complications and diabetes. We have used this model to investigate the progression of metabolic disease in a critical primate model that develops the full spectrum of the disease. Furthermore, we have used this model to investigate several different classes of therapeutics, and are currently investigating the effects of dietary supplementation to mitigate the effects of the high fat diet. In addition, we are investigating the effects of utilizing a gastric bypass procedure on obese HFD animals.
- We are interested in the metabolic adaptations of pregnancy and lactation in the adult female. These studies also use rodent and nonhuman primate models. The primary focus of these studies has been on changes in insulin and leptin sensitivity that occur during these reproductive states. These studies investigate the neurocircuitry by which leptin and insulin may regulate the hypothalamic-gonadotropin axis. A secondary focus of these studies is the possible complications during pregnancy and lactation associated with obesity, diabetes, and consumption of a high fat diet.
Dr. Kevin L. Grove has been at ONPRC since 1996, starting as a Staff Scientist. In the past 15+ years, he has developed an internationally recognized and well-funded research program focused on:
- The developmental programming of metabolic systems and how poor maternal metabolic health and diet can cause abnormalities in the developing offspring that predispose them to numerous metabolic diseases later in life.
- Interventions and therapies that can prevent or reverse the effects of diet-induced obesity/diabetes.
Both of these programs extensively use nonhuman primate (NHP) models. Dr. Grove has developed these models at ONPRC and has made them available to the broader research community, resulting in several mult-Principal Investigator and R01 grants supporting independent programs at OHSU and throughout the United States. Because of the success of the program and the emerging expertise at ONPRC and OHSU, Dr. Grove recently agreed to help develop a new division of Diabetes, Obesity, & Metabolism that is focused on metabolic diseases, and will function as the Interim Division Chief. Dr. Grove is a Senior Scientist in the Division of Diabetes, Obesity, & Metabolism, and Division of Reproductive & Developmental Sciences. He is also the Director of the NHP Obese Resource.
Dr. Grove received his BSc in the Department of Animal Science at Washington State University in 1990, and his PhD in Neuroscience from the College of Veterinary Medicine at the same university in 1994. He did his postdoctoral work at the Institute of Clinical Research of Montreal. Dr. Grove returned to the Northwest to join the ONPRC in 1996.
Brozinick, JT; Hawkins, E; Bui, HH; Kuo, MS; Tan, B; Kievit, P; Grove, KL. 2012 Plasma sphingolipids are biomarkers of metabolic syndrome in nonhuman primates maintained on a Western-style diet. Inter J Obes, In Press. PMID: 23207405. NIHMSID: 449447.
Kievit, P; Halem, H; Marks, DL; Dong, JZ; Glavas, MM; Sinnayah, P; Pranger, L; Cowley, MA; Grove, KL; Culler, MD. 2013. Chronic treatment with a melanocortin 4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques*. Diabetes. 62: 490-7. Epub 2012 Oct 9. PMCID: PMC3554387 [Available on 2014/2/1]. *Highlighted in Nature Reviews.
Lee, SJ; Kirigiti, M; Lindsley, SR; Loche, A; Madden, CJ; Morrison, SF; Smith, MS; Grove, KL. 2013. Efferent projections of NPY expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models. J Comp Neurol. 2013 Jun 1, 521: 1891-914. doi: 10.1002/cne.23265. PMCID: PMC3618613 [Available on 2013/6/1].
Comstock, SM; Pound, L; Bishop, J; Takahashi, D; Kostrba, AM; Smith, MS; Grove, KL. 2013. High-fat diet consumption during pregnancy and the early post-natal period leads to decreased cell plasticity in the nonhuman primate*. Molecular Metabolism, 2:10-22. http://dx.doi.org/10.1016/j.molmet.2012.11.001 PMCID: not available.
Fan, L; Lindsley, SR; Comstock, SM; Takahashi, DL; Evans, AE; He, GW; Thornburg, KL; Grove, KL. 2012. Maternal high-fat diet impacts endothelial function in nonhuman primate offspring. Internat. J. Obes. 37:254-62. doi: 10.1038/ijo.2012.42. Epub 2012 Mar 27. PMCID: PMC3468685.
Grant, WF; Nicol, LE; Thorn, SR; Grove, KL; Friedman, JE; Marks, DL. 2012. Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervations in one-year old male Japanese Macaques. PLoS One 7:e48119. PMCID: PMC3484148.
Frias, AE; Morgan, TK; Evans, AE; Rasanen, J; Oh, KY; Thornburg, KL; Grove, KL. 2011. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology, 152: 2456-64. PMCID: PMC3100625.
Grayson, BE; LeVasseur, P; Williams, SM, Smith, MS; Marks, DL; Grove, KL. 2010. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology, 151:1622-32. PMCID: PMC2850229.
Sullivan, EL, Grayson, BE; Takahashi, D; Robertson, N; Mairer, A; Bethea, CL; Smith, MS; Coleman, K; Grove, KL. 2010. Chronic consumption of a high fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. J. Neuroscience, 30: 3826-30. PMCID: PMC2846411.
McCurdy, CE; Bishop, J; Williams, SM; Grayson, BE; Smith, MS; Friedman, JE; Grove, KL.2009Maternal high fat diet triggers lipotoxicity in the fetal liver of the nonhuman primate. J. Clinical Invest., 119:323-35. PMCID: PMC2631287.
See a full listing of Dr. Grove's publications.