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Grizzly Bear Serum DIA Proteomics

ABSTRACT: Obesity and its accompanying metabolic complications have risen to epidemic proportions over the past 30 years. Together, these diseases are creating economic and social burdens that are expected to increase. Although multifactorial in their etiology and polygenic, the development of diseases such as metabolic syndrome in humans (obesity, fatty liver, insulin resistance [IR] and dyslipidemia) is facilitated by access to cheap, calorically dense foods. Many animal models, particularly laboratory rats and mice, have been developed to identify the underlying mechanisms involved in risk factors associated with metabolic diseases, especially Type II diabetes (T2D) and IR. Genetic models and dietary manipulations have aided our understanding of these disorders; however, it is important to recognize that examples of reversible obesity and IR occur in nature. Importantly, these conditions in animals are not associated with the negative consequences observed in humans. These observations together suggest that metabolic controls are sufficiently flexible to avoid the highly deleterious, maladapted process in humans and serve as a survival mechanism in some animals. An example of this is obesity of almost unlimited proportions (i.e., >50% body fat) and insulin resistance present in hibernating bears. Both phenotypes are reversible naturally. Our studies using cultured bear fat cells collected during hibernation recapitulate the natural insulin resistance observed in vivo. In addition, proteins or peptides found in active season serum can reverse this insulin resistance of cells from hibernating bears, indicating that circulating factors also play an important role in the seasonal modulation of insulin sensitivity. Experimentally, we can reverse the insulin resistance temporarily during hibernation by simply feeding glucose for a few weeks; thus, an important control can be added to minimize influences of body fat content, season, and diet composition. Bears therefore offer a unique model in which whole animal and cell culture systems can be used in highly standardized, easily manipulated, and controlled experiments to explore the underlying basis for reversible IR. By revealing the mechanisms involved in this reversible physiology we can gain a broader understanding of metabolic controls and the regulation of energy balance. The Washington State University (WSU) Bear Research, Education and Conservation Center is the only facility of its kind in the world dedicated to basic nutrition and physiological research using captive bears. Based on this rationale, the main objective of the proposed studies is to reveal the underlying molecular changes occurring in bears during different states of insulin sensitivity by identifying the serum proteins/peptides associated with hibernation by comparing serum from active season and hibernating bears, as well as bears that have restoring insulin sensitivity during hibernation.

ORGANISM(S): Ursus Arctos

SUBMITTER: Gennifer Merrihew

PROVIDER: PXD023555 | panorama | Wed Sep 28 00:00:00 BST 2022

REPOSITORIES: PanoramaPublic

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Grizzly Bear Serum DIA Proteomics

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