Evaluating acute inflammation’s effects on hepatic triglyceride content in experimentally induced hyperlipidemic dairy cows in late lactation

摘要

Inflammation appears to be a predisposing factorand key component of hepatic steatosis in a variety ofspecies. Objectives were to evaluate effects of inflammation[induced via intravenous lipopolysaccharide(LPS) infusion] on metabolism and liver lipid contentin experimentally induced hyperlipidemic lactatingcows. Cows (765 ± 32 kg of body weight; 273 ± 35 d inmilk) were enrolled in 2 experimental periods (P); duringP1 (5 d), baseline data were obtained. At the startof P2 (2 d), cows were assigned to 1 of 2 treatments: (1)intralipid plus control (IL-CON; 3 mL of saline; n = 5)or (2) intralipid plus LPS (IL-LPS; 0.375 μg of LPS/kgof body weight; n = 5). Directly following intravenousbolus (saline or LPS) administration, intralipid (20%fat emulsion) was intravenously infused continuously(200 mL/h) for 16 h to induce hyperlipidemia duringwhich feed was removed. Blood samples were collectedat −0.5, 0, 4, 8, 12, 16, 24, and 48 h relative to bolusadministration, and liver biopsies were obtained on d 1of P1 and at 16 and 48 h after the bolus. By experimentaldesign (feed was removed during the first 16 h of d1), dry matter intake decreased in both treatments ond 1 of P2, but the magnitude of reduction was greaterin LPS cows. Dry matter intake of IL-LPS remaineddecreased on d 2 of P2, whereas IL-CON cows returnedto baseline. Milk yield decreased in both treatmentsduring P2, but the extent and duration was longer inLPS-infused cows. Administering LPS increased circulatingLPS-binding protein (2-fold) at 8 h after bolus,after which it markedly decreased (84%) below baselinefor the remainder of P2. Serum amyloid A concentrationsprogressively increased throughout P2 in IL-LPScows (3-fold, relative to controls). Lipid infusion graduallyincreased nonesterified fatty acids and triglyceridesin both treatments relative to baseline (3- and 2.5-fold,respectively). Interestingly, LPS infusion blunted thepeak in nonesterified fatty acids, such that concentrationspeaked (43%) higher in IL-CON compared withIL-LPS cows and heightened the increase in serum triglycerides(1.5-fold greater relative to controls). Liverfat content remained similar in IL-LPS relative to P1at 16 h; however, hyperlipidemia alone (IL-CON) increasedliver fat (36% relative to P1). No treatmentdifferences in liver fat were observed at 48 h. In IL-LPScows, circulating insulin increased markedly at 4 h afterbolus (2-fold relative to IL-CON), and then graduallydecreased during the 16 h of lipid infusion. Inducinginflammation with simultaneous hyperlipidemia alteredthe characteristic patterns of insulin and LPS-bindingprotein but did not cause fatty liver.