A Rat Model of Human Lipid Emulsion Digestion

Abstract

A better understanding of how dietary lipids are processed by the human body is necessary to allow for the control of satiation and energy intake by tailored lipid systems. To examine whether rats are a valid model of human dietary lipid processing and therefore useful for further mechanistic studies in this context, we tested in rats three lipid emulsions of different stability, which alter satiety responses in humans. Different sets of 15 adult male Sprague Dawley rats, equipped with gastric catheters alone or combined with hepatic portal vein (HPV) and vena cava (VC) catheters were maintained on a medium-fat diet and adapted to an 8 h deprivation/16 h feeding schedule. Experiments were performed in a randomized cross-over study design. After gastric infusion of the lipid emulsions, we assessed gastric emptying by the paracetamol absorption test and recorded in separate experiments food intake and plasma levels of gastrointestinal hormones and metabolites in the HPV. For an acid stable emulsion, slower gastric emptying and an enhanced release of satiating gastrointestinal (GI) hormones were observed and were associated with lower short-term energy intake in rats and less hunger in humans, respectively. The magnitude of hormonal responses was related to the acid stability and redispersibility of the emulsions and thus seems to depend on the availability of lipids for digestion. Plasma metabolite levels were unaffected by the emulsion induced changes in lipolysis. The results support that structured lipid systems are digested similarly in rats and humans. Thus unstable emulsions undergo the same intragastric destabilization in both species, i.e., increased droplet size and creaming. This work establishes the rat as a viable animal model for in vivo studies on the control of satiation and energy intake by tailored lipid systems.

Keywords: animal model; energy intake; fat digestion; gastric emptying; gastrointestinal hormones; lipid emulsion systems; satiation.

Figure 1

Paracetamol plasma concentration profiles in rats after gastric infusion of 4 mL of the three different LEs. Solid and dashed lines show the group median and the individual concentration curves, respectively (LE1, acid stable LE; LE3, non-redispersible acid unstable LE with solid fat; LE4, redispersible acid unstable LE).

Figure 2

(A) Group median DOB curves and (B) parameter estimates with 95% HPD of the GLP-1, PYY, TAG, BHB, and FFA plasma concentration profiles in the hepatic portal vein (HPV) in rats after gastric infusion of 4 mL of the three different LEs. The DOB curves are grouped by LE (columns) and blood measure (rows). The concentration profiles have units ρg/mL for GLP-1 and PYY, mmol/L for TAG, μmol/L for BHB and FFA. The boxplots are grouped by parameter (rows) and blood measure (columns). The values for Amax are equal to the respective concentration profiles. The values for AOB are ρg/mL·h for GLP-1 and PYY, mmol/L·min for TAG, μmol/L·min for BHB and FFA. The value of t_max is given in min.

Figure 3

Schematic of the effects of emulsion stability and redispersibility on plasma concentration profiles of GLP-1 and PYY in rats after gastric infusion of 4 mL of the three different LEs. The arrows indicate the decrease and shift in peak concentration due to the changes in emulsion stability and redispersibility.

Figure 4

Paracetamol plasma concentration profiles in rats and gastric content emptying curves in humans after intake of the three different LEs. The data is grouped by LE (columns) and species (rows). Solid and dashed lines show the group median and individual curves, respectively.

Figure 5

(A) Estimated group average DOB curves and (B) parameter estimates of the GLP-1, PYY, TAG, BHB, and FFA plasma concentration profiles in rats and humans after intake of the three different LEs. (A) The DOB curves are grouped by LE (columns) and blood parameter (rows). Solid and dashed black lines indicate group average rat and human DOB curves, respectively. The concentration profiles have units ρg/mL for GLP-1 and PYY, mmol/L for TAG, μmol/L for BHB and FFA. (B) The boxplots are grouped by parameter (rows) and blood measure (columns). The values for Amax are equal to the respective concentration profiles. The values for AOB are ρg/mL·h for GLP-1 and PYY, mmol/L·min for TAG, μmol/L·min for BHB and FFA. The value of t_max is given in min.