Lipid Emulsion Administered Intravenously or Orally Attenuates Triglyceride Accumulation and Expression of Inflammatory Markers in the Liver of Nonobese Mice Fed Parenteral Nutrition Formula

Abstract

The accumulation of hepatic TG and development of hepatic steatosis (HS) is a serious complication of the use of parenteral nutrition (PN) formulas containing a high percentage of dextrose. But whether fat emulsions or other nutrients can ameliorate the induction of HS by high-carbohydrate diets is still uncertain. We hypothesized that administration of a lipid emulsion (LE; Intralipid) and/or the vitamin A metabolite retinal (RAL) will reduce hepatic TG accumulation and attenuate indicators of inflammation. C57BL/6 male mice were fed PN formula as their only source of hydration and nutrition for 4-5 wk. In Expt. 1, mice were fed PN only or PN plus treatment with RAL (1 μg/g orally), LE (200 μL i.v.), or both LE and RAL. In Expt. 2, LE was orally administered at 4 and 13.5% of energy to PN-fed mice. All PN mice developed HS compared with mice fed normal chow (NC) and HS was reduced by LE. The liver TG mass was lower in the PN+LE and PN+RAL+LE groups compared with the PN and PN+RAL groups (P < 0.01) and in the 4% and 13.5% PN+LE groups compared with PN alone. Hepatic total retinol was higher in the RAL-fed mice (P < 0.0001), but RAL did not alter TG mass. mRNA transcripts for fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebpf1) were higher in the PN compared with the NC mice, but FAS protein and Srebpf1 mRNA were lower in the PN+LE groups compared with PN alone. The inflammation marker serum amyloid P component was also reduced. In summary, LE given either i.v. or orally may be sufficient to reduce the steatotic potential of orally fed high-dextrose formulas and may suppress the early development of HS during PN therapy.

Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells

“…To evaluate hepatic PNPLA3 expression in response to diet, two studies were conducted. In study 1, the diet was based on a liquid formula (Clinimix E®, Baxter, Abbott, Deerfield, IL) that was supplemented with vitamins (Pediatric Influvite®, Baxter, Abbott, Deerfield, IL) and minerals and trace elements (8 μg/L zinc chloride, 6.4 μg/L cupric sulfate, 1.2 μg/L manganous sulfate, 80 μg/L chromium chloride, 176 μg/L sodium selenite, and 1.13 g/L ferrous sulfate); this HC diet has been shown to induce hepatic steatosis in 4–5 weeks (17). In study 1, twenty 5-week-old male C57BL/6 mice were housed on a 12:12 h light/dark cycle and randomized into 4 groups which received either: 1) a regular rodent diet (normal chow, rodent diet 5001 containing 58% carbohydrate, 13.5% fat, and 28.5% protein.…”

“…For all mice fed liquid diets, a known volume of the appropriate diet was added daily to a feeding tube and the amount remaining the next day was determined to calculate total intake. The liquid diet was the only source of nutrition and hydration (17). In study 2, liver tissue was obtained from a study of high fat (HF) diet-induced metabolic syndrome (18).…”

“…Mice in study 2 were housed on a 12-h light/dark cycle with free access to food and drinking water. Body weights (study 1 and 2) and liver TG levels (study 1) of mice have been published (17, 18). Briefly, final body weight among different groups were same in study 1, and exercise resulted in decreased final body weight (12%) compared to HF-fed mice.…”

Intravenous Lipid Emulsions in Parenteral Nutrition

“…Increased expression of mediators and positive regulators of de novo lipogenesis, including FA synthase and the transcription factor sterol regulatory elementbinding protein 1, has been identified in mouse models of PN-induced hepatosteatosis (13). The addition of intravenous fat to PN regimens has been shown to prevent the development of histologic hepatosteatosis (7,13) and normalize de novo lipogenesis (13) compared with formulations lacking fat in isocaloric PN administration.…”

“…Experimental evidence has suggested that in high-carbohydrate PN administration, excess acetyl-CoA generated from glucose oxidation provides substrate for upregulation fat synthesis within the liver or hepatic de novo lipogenesis (11,12). Increased expression of mediators and positive regulators of de novo lipogenesis, including FA synthase and the transcription factor sterol regulatory elementbinding protein 1, has been identified in mouse models of PN-induced hepatosteatosis (13). The addition of intravenous fat to PN regimens has been shown to prevent the development of histologic hepatosteatosis (7,13) and normalize de novo lipogenesis (13) compared with formulations lacking fat in isocaloric PN administration.…”