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Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance

  • Original Article
  • Published:
Lipids

Abstract

The progression of insulin resistance in dairy cows represents a maternal adaptation to support milk production during heightened energy demand; however, excessive adipose tissue lipolysis can develop. In diabetic non-ruminants, the mechanisms that mediate insulin resistance involve the sphingolipid ceramide. We tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. Nine dairy cows were utilized in a replicated 3 × 3 Latin square design. Cows were ad libitum fed, nutrient-restricted (NR), or NR with nicotinic acid (NA; 5 mg of NA/h per kg BW; delivered i.v.) for 34 h. When provided access, cows were ad libitum fed a mixed ration of grass hay and ground corn to meet requirements. Intake for NR cows was limited to vitamins and minerals. Nicotinic acid was administered to suppress lipolysis. Saline was infused in cows not provided NA. At 32 and 33 h of treatment, a liver biopsy and insulin tolerance test were performed, respectively. Samples were analyzed using colorimetry, immunoassay, and mass spectrometry. Nutrient restriction increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, NA infusion was unable to prevent these responses. We also show that NR increases hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0-Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In conclusion, our results suggest that ceramide accrual represents a metabolic adaptation to nutrient restriction and impaired insulin action in dairy cows.

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Abbreviations

AUC:

Area under the curve

BW:

Body weight

Cer:

Ceramide

CR:

Clearance rate

FFA:

Unesterified fatty acids

ITT:

Insulin tolerance test

NA:

Nicotinic acid

NR:

Nutrient-restricted

PDE3B:

Phosphodiesterase 3B

SPT:

Serine palmitoyltransferase

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Acknowledgements

This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2014-67016-21611 from the USDA National Institute of Food and Agriculture and the West Virginia University Ruby Distinguished Doctoral Fellows Program. We recognize Protea Biosciences (Morgantown, WV) for assisting with the mass spectrometry analysis and Vetagro, S.p.A. (Reggio Emilia, Italy) for supplying the NA. We also gratefully acknowledge Alice Mathews, J. Eduardo Rico, Sina Saed Samii, Yu Zang, and the farm staff from West Virginia University for their technical assistance.

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  1. J. W. McFadden

    Present address: Cornell University, 264 Morrison Hall, Ithaca, NY, 14853, USA

Authors and Affiliations

  1. Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, 26505, USA

    Amanda N. Davis, J. L. Clegg, C. A. Perry & J. W. McFadden

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  1. Amanda N. Davis
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  2. J. L. Clegg
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Davis, A.N., Clegg, J.L., Perry, C.A. et al. Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance. Lipids 52, 771–780 (2017). https://doi.org/10.1007/s11745-017-4287-5

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