Gelucire ®44/14 improves fat absorption in rats with impaired lipolysis

Abstract

Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire ®44/14 – a semi-solid self-micro-emulsifying excipient – could increase fat absorption. In relevant rat models for impaired lipolysis or for impaired solubilization we tested whether administration of Gelucire ®44/14 enhanced fat absorption. Rats with impaired lipolysis (lipase inhibitor Orlistat diet) and rats with reduced solubilization (permanent bile diversion) underwent a 72 h fat balance test to assess fat absorption. The absorption kinetics of a stable isotope-labeled fatty acid was assessed in rats with reduced solubilization, in the presence or absence of Gelucire ®44/14. Gelucire ®44/14 improved fat absorption in rats with impaired lipolysis (from 70% to 82%, p < 0.001). In rats with reduced solubilization, Gelucire ®44/14 did not increase fat absorption nor did it reconstitute the absorption kinetics of 13C-labeled palmitate, compared with control rats administered buffer without Gelucire ®44/14. The present data show that Gelucire ®44/14 might enhance fat absorption under conditions of impaired lipolysis, but not during impaired solubilization. We speculate that, due to its self-micro-emulsification properties, Gelucire ®44/14 stabilizes and improves residual lipolytic enzyme activity in vivo, which could be of therapeutic value in clinical conditions of fat malabsorption due to impaired lipolysis.