2,4-Thiazolidinedione in Well-Fed Lactating Dairy Goats: I. Effect on Adiposity and Milk Fat Synthesis

Abstract

Background: In a prior experiment, treatment of goats with the putative PPARγ agonist 2,4-thiazolidinedione (2,4-TZD) did not affect milk fat or expression of milk-fat related genes. The lack of response was possibly due to deficiency of vitamin A and/or a poor body condition of the animals. In the present experiment, we tested the hypothesis that PPARγ activation affects milk fat synthesis in goats with a good body condition and receiving adequate levels of vitamin A. Methods: Lactating goats receiving a diet that met NRC requirements, including vitamin A, were injected with 8 mg/kg BW of 2,4-TZD (n = 6) or saline (n = 6; CTR) daily for 26 days. Blood metabolic profiling and milk yield and components were measured including fatty acid profile. Expression of genes related to glucose and lipid metabolism was measured in adipose tissue and in mammary epithelial cells (MEC). Size of adipocytes was assessed by histological analysis. Results: NEFA, BHBA, and fatty acids available in plasma decreased while glucose increased in 2,4-TZD vs. CTR. Size of cells and expression of insulin signaling and glucose metabolism-related genes were larger in 2,4-TZD vs. CTR in adipose tissue. In MEC, expression of SCD1 and desaturation of stearate was lower in 2,4-TZD vs. CTR. Conclusions: Overall data revealed a lack of PPARγ activation by 2,4-TZD and no effect on milk fat synthesis despite a strong anti-lipolysis effect on adipose tissue.

2,4-Thiazolidinedione in Well-Fed Lactating Dairy Goats: II. Response to Intra-Mammary Infection

“…The present experiment is part of a larger project where the same animals were used to accomplish two main objectives. The first objective was to assess the effect of 2,4-TZD on milk fat synthesis [12] and the second objective was to assess the effect of 2,4-TZD on the response of goats to intramammary infection (present manuscript). See the companion manuscript [12] for overall experimental design and animal management.…”

“…The first objective was to assess the effect of 2,4-TZD on milk fat synthesis [12] and the second objective was to assess the effect of 2,4-TZD on the response of goats to intramammary infection (present manuscript). See the companion manuscript [12] for overall experimental design and animal management. Briefly, the experimental design involved injecting the treated goats daily with 8 mg of 2,4-TZD/kg of BW dissolved in 10 mL of sterile saline (TZD; n = 6) and injecting the same amount of saline only to control goats (CTR; n = 6) until the end of the trial.…”

“…Materials and methods regarding dry matter intake, milk analyses, and isolation of MEC from the milk are detailed in the companion manuscript [12].…”

“…To avoid cross-contamination, before IMI each goat was milked using one claw; after IMI both claws were used to milk one goat with one claw exclusively used to milk the right gland (i.e., the infected half) and the other claw was used to milk the healthy gland (Figure S1) of each goat. Milk yield from both halves at each milking was recorded, and milk samples were collected just before IMI, at 12 h post-IMI, and then at 1, 2, 5, 6, and 7 days post-IMI as described in the companion manuscript [12].…”

“…Collection, handling, and analysis of blood samples were as described in the companion manuscript [12]. For the present objective, samples were also collected at 12 h post-IMI and the following parameters were also measured besides glucose, non-esterified fatty acids (NEFA), triglycerides (TG), β-hydroxybutyrate (BHBA), cholesterol, creatinine, and urea [12]: inflammatory-related parameters albumin, haptoglobin, ceruloplasmin, paraoxonase, myeloperoxidase, and total bilirubin; the oxidative-related parameters total reactive oxygen metabolites (ROM), ferric reducing antioxidant power (FRAP) and Zn; plus aspartate aminotransferase, gamma-glutamyl transferase, and total protein. In addition, globulin was obtained by subtracting albumin from total protein [13].…”