Effect of crude oil extracts from trout offal as a replacement for fish oil in the diets of the Australian native fish Murray cod Maccullochella peelii peelii

The efficacy of trout oil (TO), extracted from trout offal from the aquaculture industry, was evaluated in juvenile Murray cod Maccullochella peelii peelii (25.4-0.81 g) diets in an experiment conducted over 60 days at 23.7-0.8 °C. Five isonitrogenous (48% protein), isolipidic (16%) and isoenergetic (21.8 kJ gm1) diets, in which the fish oil fraction was replaced in increments of 25% (0-100%), were used. The best growth and feed efficiency was observed in fish fed diets containing 50-75% TO. The relationship of specific growth rate (SGR), food conversion ratio (FCR) and protein efficiency ratio (PER) to the amount of TO in the diets was described in each case by second-order polynomial equations (P<0.05), which were: SGR=-0.44TO2+0.52TO+1.23 (r2=0.90, P<0.05); FCR=0.53TO2-0.64TO+1.21 (r2=0.95, P<0.05); and PER=-0.73TO2+0.90TO+1.54 (r2=0.90, P<0.05). Significant differences in carcass and muscle proximate compositions were noted among the different dietary treatments. Less lipid was found in muscle than in carcass. The fatty acids found in highest amounts in Murray cod, irrespective of the dietary treatment, were palmitic acid (16:0), oleic acid (18:1n-9), linoleic acid (18:2n-6) and eicosapentaenoic acid (20:5n-3). The fatty acid composition of the muscle reflected that of the diets. Both the n-6 fatty acid content and the n-3 to n-6 ratio were significantly (P<0.05) related to growth parameters, the relationships being as follows. Percentage of n-6 in diet (X) to SGR and FCR: SGR=-0.12X2+3.96X-32.51 (r2=0.96) and FCR=0.13X2-4.47X+39.39 (r2=0.98); and n-3:n-6 ratio (Z) to SGR, FCR, PER: SGR=-2.02Z2+5.01Z-1.74 (r2=0.88), FCR=2.31Z2-5.70Z+4.54 (r2=0.93) and PER=-3.12Z2-7.56Z+2.80 (r2=0.88) respectively. It is evident from this study that TO could be used effectively in Murray cod diets, and that an n-3:n-6 ratio of 1.2 results in the best growth performance in Murray cod.

Pituitary adenylate cyclase-activating polypeptide induces translocation of its G-protein-coupled receptor into caveolin-enriched membrane microdomains, leading to enhanced cyclic AMP generation and neurite outgrowth in PC12 cells

Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin/glucagon/vasoactive intestinal peptide family expressed throughout the nervous system, binds to the PACAP-specific G-protein-coupled receptor family members to promote both neuronal differentiation and survival. Although the PACAP receptor is known to activate its effector protein, adenylate cyclase (AC), and thus enhance cAMP generation, the molecular mechanism utilized by the receptor to activate AC is lacking. Here, we show that PACAP induces neurite outgrowth in PC12 cells by induction of translocation of the PACAP type 1 receptor (PAC1R) into caveolin-enriched Triton X-100-insoluble microdomains, leading to stronger PAC1R-AC interaction and elevated cAMP production. Moreover, we demonstrate that translocation of PAC1R is blocked by various treatments that selectively disrupt caveolae. As a result, intracellular cAMP level is decreased and consequently the PACAP-induced neurite outgrowth retarded. In contrast, addition of exogenous ganglioside GM1 to the cells shows the opposite effects. These results therefore identify the PACAP-induced translocation of its G-protein-coupled receptor into caveolae, where both AC and the regulating G-proteins reside, as the key molecular event in activating AC and inducing cAMP-mediated differentiation of PC12 cells.

Lipids in Amyloid-β processing, aggregation, and toxicity

Aggregation of amyloid-beta (Aβ) peptide is the major event underlying neuronal damage in Alzheimer's disease (AD). Specific lipids and their homeostasis play important roles in this and other neurodegenerative disorders. The complex interplay between the lipids and the generation, clearance or deposition of Aβ has been intensively investigated and is reviewed in this chapter. Membrane lipids can have an important influence on the biogenesis of Aβ from its precursor protein. In particular, increased cholesterol in the plasma membrane augments Aβ generation and shows a strong positive correlation with AD progression. Furthermore, apolipoprotein E, which transports cholesterol in the cerebrospinal fluid and is known to interact with Aβ or compete with it for the lipoprotein receptor binding, significantly influences Aβ clearance in an isoform-specific manner and is the major genetic risk factor for AD. Aβ is an amphiphilic peptide that interacts with various lipids, proteins and their assemblies, which can lead to variation in Aβ aggregation in vitro and in vivo. Upon interaction with the lipid raft components, such as cholesterol, gangliosides and phospholipids, Aβ can aggregate on the cell membrane and thereby disrupt it, perhaps by forming channel-like pores. This leads to perturbed cellular calcium homeostasis, suggesting that Aβ-lipid interactions at the cell membrane probably trigger the neurotoxic cascade in AD. Here, we overview the roles of specific lipids, lipid assemblies and apolipoprotein E in Aβ processing, clearance and aggregation, and discuss the contribution of these factors to the neurotoxicity in AD.