Research Article Details
| Article ID: | A43604 |
| PMID: | 31301829 |
| Source: | J Dairy Sci |
| Title: | Invited review: Sphingolipid biology in the dairy cow: The emerging role of ceramide. |
| Abstract: | The physiological control of lactation through coordinated adaptations is of fundamental importance for mammalian neonatal life. The putative actions of reduced insulin sensitivity and responsiveness and enhanced adipose tissue lipolysis spare glucose for the mammary synthesis of milk. However, severe insulin antagonism and body fat mobilization may jeopardize hepatic health and lactation in dairy cattle. Interestingly, lipolysis- and dietary-derived fatty acids may impair insulin sensitivity in cows. The mechanisms are undefined yet have major implications for the development of postpartum fatty liver disease. In nonruminants, the sphingolipid ceramide is a potent mediator of saturated fat-induced insulin resistance that defines in part the mechanisms of type 2 diabetes mellitus and nonalcoholic fatty liver disease. In ruminants including the lactating dairy cow, the functions of ceramide had remained virtually undescribed. Through a series of hypothesis-centered studies, ceramide has emerged as a potential antagonist of insulin-stimulated glucose utilization by adipose and skeletal muscle tissues in dairy cattle. Importantly, bovine data suggest that the ability of ceramide to inhibit insulin action likely depends on the lipolysis-dependent hepatic synthesis and secretion of ceramide during early lactation. Although these mechanisms appear to fade as lactation advances beyond peak milk production, early evidence suggests that palmitic acid feeding is a means to augment ceramide supply. Herein, we review a body of work that focuses on sphingolipid biology and the role of ceramide in the dairy cow within the framework of hepatic and fatty acid metabolism, insulin function, and lactation. The potential involvement of ceramide within the endocrine control of lactation is also considered. |
| DOI: | 10.3168/jds.2018-16095 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |