REGULATION OF LIPOGENESIS BY SPARED NUTRIENTS IN THE BOVINE MAMMARY AND ADIPOSE TISSUE

Abstract

Optimization of milk fat synthesis is important to nutritionists, farmers, and the dairy industry because of the high market value and intrinsic properties of milk for manufacturing dairy products. Milk fat depression (MFD) is a condition caused by altered rumen fermentation when highly fermentable diets are fed and, although it is normally not desired, has been extensively investigated to understand the mechanisms regulating fat synthesis in the mammary gland. Milk fat depression can be experimentally induced using trans-10, cis-12 conjugated linoleic acid (CLA), the most potent trans-FA inhibitor of milk fat synthesis identified. On farm use of CLA-induced MFD has been proposed to benefit high producing and transition cows that undergo a profound negative energy balance due to massive mobilization of body fat stores to support milk synthesis. The mechanism involves decreased use of dietary nutrients for milk fat synthesis which improves energy balance and reduces the use of body fat stores for milk synthesis. However, significant confusion about the effect of spared nutrients and CLA on adipose and mammary lipogenesis exists. The objective of experiments presented in this dissertation was to investigate the role of nutrients spared from milk fat synthesis during CLA-induced MFD on adipose and mammary lipogenesis. Acetate was used as a spared nutrient, because it is the main nutrient spared during MFD. The first experiment aimed to investigate the direct effect and interaction of CLA and spared nutrients on adipose lipogenesis in non-lactating cows. In this experiment we found that adipose tissue is sensitive to the anti-lipogenic effects of trans-10, cis-12 CLA at the transcription level, as expression of the lipogenic transcription factors SREBP1 and PPARγ2, and of the lipogenic enzymes FASN, ACC, SCD and LPL were reduced by CLA (all P < 0.05). However adipose lipogenic capacity was not affected by CLA. Acetate tended to reduce expression of lipogenic factors Spot 14 and PPARγ1 (P = 0.07) and reduced expression of FAN, ACC, and SCD (P < 0.05), but did not affect adipose lipogenesis capacity. In a second experiment, the direct effect of CLA and spared acetate on adipose lipogenesis in lactating cows was tested. Here, CLA reduced lipogenic capacity by 70%, with no changes in expression of lipogenic factors or enzymes. Additionally, acetate did not affect adipose lipogenesis; however, milk fat yield increased by 20% when spared acetate was provided (424 g of acetate/d), suggesting that acetate might me limiting milk fat synthesis under normal dietary conditions. The last experiment investigated the dose relationship between acetate supply and milk fat synthesis in cows with normal milk fat levels. Importantly, acetate linearly increased milk fat concentration from 3.71% in control to 4.12% at the highest dose of acetate (P < 0.01) and quadratically increased milk fat yield up to 217 g/d with an acetate dose of 10 moles/d (P < 0.001). In conclusion, adipose tissue is sensitive to the anti-lipogenic effects of trans-10, cis-12 CLA , while acetate spared during CLA-induced MFD does not play a role in stimulating adipose lipogenesis. However, under normal dietary conditions, acetate stimulates mammary lipogenesis. Together, these experiments provide key insights to the effect of CLA on adipose tissue lipogenesis and the role of spared acetate on adipose and mammary lipogenesis.