Dataset Information

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

ABSTRACT: GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.

SUBMITTER: Patel S

PROVIDER: S-EPMC6408327 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

Patel Satish S Alvarez-Guaita Anna A Melvin Audrey A Rimmington Debra D Dattilo Alessia A Miedzybrodzka Emily L EL Cimino Irene I Maurin Anne-Catherine AC Roberts Geoffrey P GP Meek Claire L CL Virtue Samuel S Sparks Lauren M LM Parsons Stephanie A SA Redman Leanne M LM Bray George A GA Liou Alice P AP Woods Rachel M RM Parry Sion A SA Jeppesen Per B PB Kolnes Anders J AJ Harding Heather P HP Ron David D Vidal-Puig Antonio A Reimann Frank F Gribble Fiona M FM Hulston Carl J CJ Farooqi I Sadaf IS Fafournoux Pierre P Smith Steven R SR Jensen Jorgen J Breen Danna D Wu Zhidan Z Zhang Bei B BB Coll Anthony P AP Savage David B DB O'Rahilly Stephen S

Cell metabolism 20190110 3

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, ...[more]

PMID: 30639358

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Project description:Eggshells are significant part of hatchery waste which consist of calcium carbonate crust, membranes, and proteins and peptides of embryonic origins along with other entrapped contaminants including microbes. We hypothesized that using this product as a nutritional additive in poultry diet may confer better immunity to the chickens in the paradigm of mammalian milk that enhances immunity. Therefore, we investigated the effect of hatchery eggshell membranes (HESM) as a short term feed supplement on growth performance and immunity of chickens under bacterial lipopolysaccharide (LPS) challenged condition. Three studies were conducted to find the effect of HESM supplement on post hatch chickens. In the first study, the chickens were fed either a control diet or diets containing 0.5% whey protein or HESM as supplement and evaluated at 5 weeks of age using growth, hematology, clinical chemistry, plasma immunoglobulins, and corticosterone as variables. The second and third studies were done to compare the effects of LPS on control and HESM fed birds at 5 weeks of age following at 4 and 24 h of treatment where the HESM was also sterilized with ethanol to deplete bacterial factors. HESM supplement caused weight gain in 2 experiments and decreased blood corticosterone concentrations. While LPS caused a significant loss in body weight at 24 h following its administration, the HESM supplemented birds showed significantly less body weight loss compared with the control fed birds. The WBC, heterophil/lymphocyte ratio, and the levels of IgG were low in chickens fed diets with HESM supplement compared with control diet group. LPS challenge increased the expression of pro-inflammatory cytokine gene IL-6 but the HESM fed birds showed its effect curtailed, also, which also, favored the up-regulation of anti-inflammatory genes compared with control diet fed chickens. Post hatch supplementation of HESM appears to improve performance, modulate immunity, and increase resistance of chickens to endotoxin.

Dataset Information

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

Publications

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

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