Free Fatty Acids Treatment Research Articles

Ruminal Fermentation and Amino Acid Flow in Holstein Steers Fed Whole Cottonseed with Elevated Concentrations of Free Fatty Acids in the Oil

The influence of feeding whole cottonseed (WCS) containing elevated concentrations of free fatty acids (FFA) in the oil on ruminal fermentation and amino acid (AA) flow to the abomasum was evaluated in a 4×4 Latin square trial. Four ruminally and abomasally cannulated Holstein steers were fed diets containing 12.5% of dry matter as WCS with concentrations of 8.0, 11.3, 14.7, or 18.0% FFA in the oil. Intake, ruminal digestibility, and flow to the abomasum of dry matter, organic matter, and acid detergent fiber were not affected by FFA level of WCS. Intake of neutral detergent fiber and total kilograms of neutral detergent fiber digested in the rumen were similar for all treatments. Ruminal neutral detergent fiber digestibility was lower for 8 and 14.7% FFA, resulting in a cubic effect on flow to the abomasum. Ruminal pH, molar proportions of isobutyrate, and total branched-chain volatile fatty acids (VFA) decreased linearly, whereas molar proportions of acetate and acetate:propionate ratio increased linearly as FFA in WCS increased. Total VFA were lower, and molar proportions of propionate were higher, for 8 and 14.7% FFA, resulting in a cubic effect. Intake of N, total N flow, and nonmicrobial N flow to the abomasum were similar among treatments. Flow of microbial N was lower for the 11.3% FFA treatment, resulting in a quadratic response. Only nonsignificant differences were observed in AA flow to the abomasum. Results of this trial indicate that WCS with FFA up to 18% may result in small changes in rumen fermentation.

Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway.

Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor kappa B-dependent tumor necrosis factor alpha expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated "dysmetabolic syndrome." In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization.

Intracellular depletion of insulin: a comparative study with palmitate, oleate and elaidate in INS-1 cells.

Free fatty acids (FFAs) deplete the intracellular insulin stores of pancreatic beta-cells. It has been suggested that this results from a lipotoxic dysregulation of both insulin secretion and insulin synthesis. In the present study, this hypothesis was tested within a 12-h time-course by directly relating the FFA-induced loss of intracellular insulin to corresponding parameters of insulin secretion and de novo biosynthesis. Palmitate, cis-monoenic oleate and the trans-monoenic elaidate were employed as model FFAs to elucidate potentially different effects due to chain length and configuration. INS-1 cells were incubated for 1, 4 or 12 h with 11.2 mmol/l glucose with 200 micromol/l palmitate, oleate or elaidate and compared with non-FFA-exposed controls with respect to content and secretion of immunoreactive insulin (IRI). Biosynthesis of insulin was monitored by pulse-labeling experiments and by Northern blot analysis. IRI content dropped by 50-60% after a short-term exposure with all FFAs employed (P< or =0.001). It tended to recover after 12 h of treatment with oleate and elaidate but not with palmitate. FFA treatment increased insulin secretion by 25% (P< or =0.05) which could not account quantitatively for the intracellular loss. FFA-induced changes in insulin biosynthesis did not correlate clearly with the FFA-induced intracellular loss. The FFA-induced loss of IRI is an acute effect independent of the FFA employed. It cannot be sufficiently explained by FFA-induced perturbances of IRI secretion and biosynthesis. We therefore postulate an additional FFA-triggered mechanism, e.g. intracellular IRI degradation.

Serum Glucose and Free Fatty Acids Modulate Growth Hormone and Luteinizing Hormone Secretion in the Pig

Two experiments were conducted to determine the effect of free fatty acids (FFA) and glucose treatment on growth hormone (GH) and luteinizing hormone secretion in the pig. In Experiment (Exp) 1, 15 prepuberal gilts received an intravenous infusion of FFA (n = 5; 3 ml of 10% Liposyn II/kg), glucose (n = 5; 1 g/kg), or saline (n = 5; 3 ml of 0.9%/kg). Jugular blood samples were collected every 15 min for 2 hr before and 3 hr after intravenous infusion of saline, FFA, and glucose. Synthetic [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (1 microgram/kg) and gonadotropin-releasing hormone (0.2 micrograms/kg) were administered 30 min after infusion (Time 0 = infusion). In Exp 2, eight prepuberal gilts received either FFA (n = 4) or saline (n = 4) as described in Exp 1, except that treatments were given every hour ove a 10-hr period. Blood samples were collected every 15 min from 1 hr before to 10 hr after the start of FFA or saline infusion. In Exp 1, the peak GH response to growth hormone-releasing factor was delayed by 45 min (P less than 0.01) by glucose treatment and suppressed (P less than 0.01) by FFA treatment. The luteinizing hormone response to gonadotroph-releasing hormone was suppressed (P less than 0.03) by glucose and enhanced (P less than 0.03) by FFA. In Exp 2, the number of GH pulses was increased (P less than 0.05) by FFA infusion and GH concentrations were positively correlated (r = 0.58, P less than 0.0003) with FFA concentrations, while luteinizing hormone pulse amplitude was greater (P less than 0.01) in FFA gilts than in saline gilts. These results indicate that FFA are more effective modulators of GH secretion than acute hyperglycemia, while metabolic status can alter pituitary responsiveness to gonadotropin-releasing hormone.

Influence of fatty acids on ammonia and amino acid flux from active human muscle

This study examined the dynamics of ammonia and amino acid exchange of human muscle during prolonged steady-state one-legged exercise at 80% of knee extensor maximal work capacity. Subjects (n = 10) performed leg extensor exercise for 1 h (control series), rested for 40 min while an infusion of Intralipid and heparin was begun, and then exercised the contralateral leg with the identical protocol [free fatty acid (FFA) series]. In the control series, ammonia efflux rose progressively, and 4.4 +/- 0.6 mmol were released in 1 h compared with 2.4 +/- 0.5 mmol (P less than 0.05) in the FFA series. The exercise was associated with large effluxes of total amino acids from the active muscle over the hour (12.8 +/- 4.3 and 10.3 +/- 3.3 mmol for control and FFA, respectively). Glutamine and alanine accounted for 47 and 64% of the efflux for the control and FFA series, respectively, while comparable values for essential amino acids were 24 and 20%. The latter implies that a net muscle protein catabolism was occurring during the exercise. The FFA treatment was associated not only with a reduced muscle ammonia release but also with a decreased (P less than 0.05) arterial concentration of nine amino acids (alanine, methionine, lysine, hydroxyproline, serine, glycine, proline, asparagine, and ornithine). Interpretation is limited due to the treatment order effect, but these data are compatible with the hypothesis that plasma clearance was affected by FFA.