RETRACTED: Grizzly Bears Exhibit Augmented Insulin Sensitivity while Obese Prior to a Reversible Insulin Resistance during Hibernation

Nelson, O. Lynne; Jansen, Heiko T.; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, J L; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J.; Vella, Chantal; Robbins, Charles T.; Corbit, Kevin C.

doi:10.1016/j.cmet.2014.07.008

Cited by 29 publications

(27 citation statements)

References 32 publications

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“…97). Recent data show that hibernating grizzly bears respond to insulin in the spring and autumn, but not during the hibernation season (207). Clearly, this is a fruitful area for future research.…”

Section: Food Quantity and Qualitymentioning

confidence: 99%

Metabolic Flexibility: Hibernation, Torpor, and Estivation

Staples

2016

Comprehensive Physiology

136

116

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Many environmental conditions can constrain the ability of animals to obtain sufficient food energy, or transform that food energy into useful chemical forms. To survive extended periods under such conditions animals must suppress metabolic rate to conserve energy, water, or oxygen. Amongst small endotherms, this metabolic suppression is accompanied by and, in some cases, facilitated by a decrease in core body temperature-hibernation or daily torpor-though significant metabolic suppression can be achieved even with only modest cooling. Within some ectotherms, winter metabolic suppression exceeds the passive effects of cooling. During dry seasons, estivating ectotherms can reduce metabolism without changes in body temperature, conserving energy reserves, and reducing gas exchange and its inevitable loss of water vapor. This overview explores the similarities and differences of metabolic suppression among these states within adult animals (excluding developmental diapause), and integrates levels of organization from the whole animal to the genome, where possible. Several similarities among these states are highlighted, including patterns and regulation of metabolic balance, fuel use, and mitochondrial metabolism. Differences among models are also apparent, particularly in whether the metabolic suppression is intrinsic to the tissue or depends on the whole-animal response. While in these hypometabolic states, tissues from many animals are tolerant of hypoxia/anoxia, ischemia/reperfusion, and disuse. These natural models may, therefore, serve as valuable and instructive models for biomedical research.

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Section: Food Quantity and Qualitymentioning

confidence: 99%

Metabolic Flexibility: Hibernation, Torpor, and Estivation

Staples

2016

Comprehensive Physiology

136

116

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“…One condition in which specifi c organisms are challenged with prolonged fasting is hibernation. A recent study has demonstrated that during hibernation, grizzly bears exhibit reversible insulin resistance coupled with elevated lipolysis and markedly increased aP2 expression, and their glucose levels are well maintained at this stage ( 60 ). In the posthibernation period when bears are no longer reliant on fat stores, adipose aP2 levels are dramatically decreased and insulin sensitivity is increased.…”

Section: Downloaded Frommentioning

confidence: 99%

Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity

Ertunc

Sikkeland

Fenaroli

et al. 2015

Journal of Lipid Research

127

172

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Journal of Lipid Research Volume 56, 2015 423Adipose tissue is an endocrine organ whose products orchestrate the metabolic functions of various tissues, including brain, pancreas, and liver, to maintain systemic homeostasis. Adipocytes respond to metabolic and immune cues by mobilizing their fat stores through lipolysis and by secreting a variety of hormones and cytokines ( 1, 2 ). Such signals converge on target tissues, for example on liver to regulate glucose production, and on ␤ cells to modulate insulin production. A critical molecule for the integration of adipocyte biology with systemic metabolic regulation is aP2 [fatty acid binding protein (FABP) 4], a lipid binding protein that is upregulated during differentiation of adipocytes and upon macrophage activation ( 3, 4 ). Since its identifi cation, aP2 has been studied primarily for its intracellular functions in lipid metabolism and infl ammation ( 3,4 ). Genetic deletion models demonstrated that this FABP plays a critical role in the pathogenesis of several chronic metabolic diseases, including diabetes, atherosclerosis, and fatty liver. Mice defi cient in aP2 or aP2 and the related protein FABP5/mal1 together have improved adipose and liver function, increased insulin sensitivity, and reduced fatty liver and cardiovascular disease in the context of high-fat diet and genetic mouse models of obesity and atherosclerosis ( 5-12 ). The link between aP2 and metabolic disease is also supported by genetic association studies in multiple populations demonstrating metabolic and cardiovascular benefi ts in individuals carrying a rare haploinsuffi ciency mutation in the aP2 locus, validating the relevance of this pathway in human disease ( 13,14 ).

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“…Similarly humans with haplo-insufficiency due to mutations in PTEN were found to have enhanced insulin sensitivity [48]. Recently an increase in insulin sensitivity due to suppression of PTEN has been described in grizzly bears in preparation for hibernation, indicating that this is a mechanism for physiological adaptation [49].…”

Section: Phosphatase and Tensin Homolog (Pten)mentioning

confidence: 99%