Lipid modulation of insulin resistance in Holstein cows

The overall objective was to study the relationship between blood lipids and insulin resistance in Holstein cows. Specific objectives were to address whether elevated plasma nonesterified fatty acid (NEFA) concentration is a causal factor of insulin resistance and whether manipulation of blood serum fatty acid profile alters whole body responses to insulin in Holstein cows. Two experimental approaches were developed to investigate the relationship between elevated plasma NEFA and insulin resistance: induction of hyperlipidemia using intravenous infusions of a tallow derived emulsion in fed animals, and reduction of plasma NEFA concentration using nicotinic acid (NA) as an antilipolytic agent in feed restricted cows. Induction of hyperlipidemia by intravenous infusion of tallow-derived emulsion caused insulin resistance in Holstein cows. Further experiments assessed the effects of manipulation of blood serum fatty acid composition on responses to insulin. Fatty acid profile was changed by abomasal infusions of linseed oil, which is a source rich in o-3 linolenic acid. Results suggest that infusion of linseed oil increased the response to insulin in fed cows and may have enhanced the antilipolytic effects of insulin in feed restricted cows. However data must be interpreted with caution because for unknown reasons plasma NEFA concentrations immediately before glucose and insulin challenges was approximately 100 muEq/L greater for linseed oil than tallow. A methodology involving abomasal infusions of NA as antilipolytic agent was developed to decrease plasma NEFA concentration in feed-restricted Holstein cows. Employment of this approach showed that reduction of plasma NEFA concentration enhances the response to insulin in feed-restricted cows. These results establish a cause-effect relationship between elevated plasma NEFA and insulin resistance in Holstein cows. The induction of insulin resistance by NEFA may add to other homeorhetic signals that direct glucogenic nutrients to vital functions, conceptus, and mammary gland. However, NEFA-induced insulin resistance may also be a key feature in the maladaptation to energy metabolism in the periparturient dairy cow. Since impaired insulin signaling affects an array of cell functions, NEFA-induced insulin resistance may have important repercussions on the physiology and productivity of the periparturient dairy cow.