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 health care costs associated with adult obesity exceed a hundred billion dollars annually; 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 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 life-style 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).
1) 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.
2) 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.
3) 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.
BIOGRAPHY
Kevin Grove is a Senior Scientist in the Division of Neuroscience and Division of Reproductive & Developmental Sciences, and is the Director of the Metabolic Disease Working Group and Director of the Obese NHP Resource. 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. Grove returned to the Northwest to join the ONPRC Division of Neuroscience in 1996.
KEY PUBLICATIONS
McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE*, Grove KL*. (2009) Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest 119:323-335.
Sullivan EL, Grayson BE, Takahashi D, Robertson N, Maier 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 Neurosci 30:3826-3830.
Glavas MM, Kirigiti MA, Xiao XQ, Enriori PJ, Fisher SK, Evans AE, Grayson BE, Cowley MA, Smith MS, Grove KL. (2010) Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet. Endocrinology 151:1598-1610.
True C, Kirigiti M, Ciofi P, Grove KL, Smith MS. (2011) Characterization of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. J. Neuroendocrinol. 23: 52-64.
Suter M, Bocock P, Showalter L, Hu M, Shope C, McKnight R, Grove K, Lane R, Aagaard-Tillery K. (2011) Epigenomics: Maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J., 25: 714-26
Grant WF, Gillingham MB, Batra AK, Fewkes NM, Comstock SM, Takahashi D, Braun TP, Grove KL, Friedman JE, Marks DL. (2011) Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates. PLoS One. 6:e17261.
See a full listing of Dr. Grove's publications.
