Mechanism of Adipose Tissue Specific Response to Heat Stress in Pigs
Heat stress (HS) is a major problem facing the swine industry all over the world, especially during the hot summer months. The two major reasons pigs are highly susceptible to elevated ambient temperature are that they have substantial subcutaneous fat layer that serves as a barrier against effective heat dissipation and their lack of functional sweat glands on their skin surface for evaporative heat loss. Paradoxically, HS results in increased fat deposition in pigs. However, the fundamental causes of the increased adiposity during HS are unknown. Therefore, we conducted several in vivo and in vitro experiments to elucidate the precise mechanisms of HS response in pig adipose tissue. In the first study, we used an in vitro adipocyte differentiation model to characterize cellular responses that occur during differentiation of pig adipocytes in HS. We found the existence of cell autonomous response to HS in pig adipocytes that results in increased adipocyte lipid storage. In the second study, we wanted to elucidate the mechanisms of HS management and their relationship to adipose tissue metabolism. Thirty cross-bred (Ossabaw × Duroc × Landrace) pigs (boars n=15, gilts n=15) were assigned to three treatments for 1 week: 1) control and libitum fed (CON) with environment temperature 20 °C ± 1 °C and ad libitum access to feed, 2) pair-fed (PF) with environment temperature 20 °C ± 1 °C and fed the amount same as HS pigs, 3) HS with environment temperature 35 °C ± 1 °C and ad libitum access to feed. Heat stress led to increased glyceroneogenesis accompanied by induction of phosphoenolpyruvate carboxykinase (PCK1) in adipose tissue without alteration of serum glucose, insulin, FFA and triglyceride concentrations and this revealed that glyceroneogenesis, perhaps through PCK1, plays an important role in increased adipose lipid storage under HS. In the third experiment, we used a commercial-type pig genotype, a Duroc × Yorkshire × Landrace terminal cross, to evaluate effects of both acute (24 h) and chronic (7 d) HS on gene expression responses in adipose and other peripheral tissues. The HS induced a robust adipose tissue response in favor of increased lipid storage. This indicates that adipose tissue might play an important role in HS adaptation, irrespective of the genotype of the pig. In the fourth study, the effect of PCK1 inhibition with 3 mercaptopicolinic acid (3MPA) on lipid storage and adipocyte response during HS was investigated. Inhibition of PCK1 during HS, adipocytes were less able to induce adaptive responses such as upregulation of HSP70 and triglycerides, and this exacerbated endoplasmic reticulum (ER) stress during HS. Therefore, PCK1 may function to alleviate ER stress that occurs during HS. In the fifth study, we wanted to determine global changes in adipose tissue and adipocyte metabolites and lipids species to see if they could serve as useful biomarkers that could be associated with HS adaptation response. Using metabolomics, lipidomics, and fatty acid profile analysis with gas chromatography, we found that HS induced distinct metabolite profiles. This may have implications for the explanation of the regulation of lipogenesis, fatty acid oxidation and membrane fluidity in adipose tissue during HS. Overall, these studies indicate a potential major role for PCK1 in the increased lipid storage during HS and in the suppression of ER stress that may occur in adipose tissue during HS. Thus, the increased lipid storage in adipose tissue during HS might be a protective mechanism against excessive ER stress and adipocyte death in this tissue.
Ajuwon, Purdue University.
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