Kevin Grove

As a major contributor to the increased occurrence of coronary heart disease and type II (juvenile) diabetes, obesity is now considered a worldwide health concern. The latest data indicate that almost two-thirds of Americans are overweight. Even more disturbing and more devastating to the future of human health is the dramatic increase in juvenile/adolescent obesity. In the United States, more than 15 percent of 6- through 19-year-olds and more than 10 percent of 2- through 5-year-olds are classified as obese because they have a body mass index (BMI) at or above the 95th percentile. Finally, almost 12 percent of children between the ages of 6 and 23 months are classified as obese. The dramatic increase in this statistic is of grave concern because early onset obesity greatly increases the risk of persistent obesity and obesity related health risks (Syndrome X). Ten years ago juvenile type II diabetes was rarely heard of; now it is becoming a serious medical threat.

The Grove laboratory has several research areas focused around around the regulation energy homeostasis including the investigation of the progression of metabolic disease as well as therapeutic interventions. All of the studies in our group involve both rodent (rat and mouse) and nonhuman primates.

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 is that chronic consumption of a high fat/calorie diet 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 (35% calories from fat diet). Over several years 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.

3) We are interested in the metabolic adaptations 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 are the possible complications during pregnancy and lactation associated with obesity, diabetes and consumption of a high fat diet.

BIOGRAPHY

Kevin Grove is an associate scientist in the Division of Neuroscience and is the Co-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

Melnick, I; Pronchuk, N; Cowley, MA; Grove, KL*; Colmers, MF* (2007) Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus. Neuron, 56:1103-1115.  PMID:18093530.

Enriori, PJ; Evans, AE; Sinnayah, P; Jobst, EE; Tonelli-Lemos, L; Billes, SK; Glavas, MM; Grayson BE, Perello, M; Nillni, EA; Grove, KL; Cowley, MA. (2007) Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metabolism 5:181-194. PMID:17339026.

Xiao, XQ; Williams, S; Grayson, BE; Glavas, MM; Cowley, MA; Smith, MS; Grove, KL. (2007) Excess weight gain during the early postnatal period is associated with permanent reprogramming of brown adipose tissue adaptive thermogenesis. Endocrinology, 148:4150-4159.  PMID:17525123.

Glavas, M; Grayson, BE; Allen, S; Billes, S; Smith, MS; Cowley, MA; Grove, KL. (2008) Characterization of brainstem peptide YY (PYY) neurons. Journal of Comparative Neurology 506:194-210.  PMID:18022952.

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.  Journal of Clinical Investigation 119:323-335. PMID:19147984.