Relationship between carcass weight, adipose tissue androstenone level and expression of the hepatic 3β-hydroxysteroid dehydrogenase in entire commercial pigs

Boar taint is a major meat-quality defect in pigs and is due to excessive accumulation of skatole and androstenone in adipose tissue. The present work investigated the relationship between carcass weight, levels of skatole and androstenone in adipose tissue, and expression of the hepatic androstenone-metabolising enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), in 22 entire male and 22 entire female crossbred pigs (Large White (40%) × Landrace (40%) × Duroc (20%)). Animals of each gender were divided into two subgroups (11 pigs in each subgroup): (i) conventional weight (carcass weight 59 to 77 kg) and (ii) heavy weight (carcass weight 84 to 95 kg). No relationship between carcass weight and adipose tissue skatole level was found for entire male pigs (r2 = 0.013, P > 0.05). There was a significant negative relationship between carcass weight and expression of the hepatic 3β-HSD protein (r2 = 0.502, P < 0.001) and a significant negative relationship between 3β-HSD protein expression and androstenone level in adipose tissue (r2 = 0.24, P < 0.05) in entire males. No relationship was found between carcass weight and 3β-HSD protein expression in female pigs (r2 = 0.001, P > 0.05). 3β-HSD expression was 59% higher in conventional-weight male pigs when compared with heavy-weight animals (P < 0.05) and 36% higher in heavy-weight females when compared with heavy-weight males (P < 0.05). It is concluded that an increase in slaughter weight of entire commercial crossbred Large White pigs is accompanied by inhibition of expression of the hepatic 3β-HSD protein, which might result in a reduced rate of hepatic androstenone clearance with its subsequent accumulation in adipose tissue. It is suggested that regulation of pig hepatic 3β-HSD expression is under the control of sex hormones.     

Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects

Objective: We previously reported that a single preprandial injection (120 μg) of pramlintide, an analog of the β‐cell hormone amylin, reduced ad libitum food intake in obese subjects. To further characterize the meal‐related effects of amylin signaling in humans, we studied a lower pramlintide dose (30 μg) in normal‐weight subjects. Research Methods and Procedures: In a randomized, double‐blind, placebo‐controlled, cross‐over study, 15 healthy men (age, 24 ± 7 years; BMI, 22.2 ± 1.8 kg/m²) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 μg) or placebo, followed immediately by a standardized pre‐load meal. After 1 hour, subjects were offered an ad libitum buffet meal, and total caloric intake and meal duration were measured. Results: Compared with placebo, pramlintide reduced total caloric intake (1411 ± 94 vs. 1190 ± 117 kcal; Δ, ?221 ± 101 kcal; ?14 ± 9%; p = 0.05) and meal duration (36 ± 2 vs. 31 ± 3 minutes; Δ, ?5.1 ± 1.4 minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and fullness higher during the first hour after pramlintide administration. In response to the buffet, hunger and fullness changed to a similar degree after pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer kilocalories. Visual analog scale nausea ratings remained near baseline, without differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin concentrations did not differ with treatment, whereas glucagon‐like peptide‐1 concentrations after meals were lower in response to pramlintide than to placebo. Discussion: These observations add support to the concept that amylin agonism may have a role in human appetite control.     

Turn nucleation perturbs amyloid β self-assembly and cytotoxicity

The accumulation of senile plaques composed of amyloid β (Aβ) fibrils is a hallmark of Alzheimer's disease, although prefibrillar oligomeric species are believed to be the primary neurotoxic congeners in the pathogenesis of Alzheimer's disease. Uncertainty regarding the mechanistic relationship between Aβ oligomer and fibril formation and the cytotoxicity of these aggregate species persists. β-Turn formation has been proposed to be a potential rate-limiting step during Aβ fibrillogenesis. The effect of turn nucleation on Aβ self-assembly was probed by systematically replacing amino acid pairs in the putative turn region of Aβ (residues 24-27) with d-ProGly ((D)PG), an effective turn-nucleating motif. The kinetic, thermodynamic, and cytotoxic effects of these mutations were characterized. It was found that turn formation dramatically accelerated Aβ fibril self-assembly dependent on the site of turn nucleation. The cytotoxicity of the three (D)PG-containing Aβ variants was significantly lower than that of wild-type Aβ40, presumably due to decreased oligomer populations as a function of a more rapid progression to mature fibrils; oligomer populations were not eliminated, however, suggesting that turn formation is also a feature of oligomer structures. These results indicate that turn nucleation is a critical step in Aβ40 fibril formation.     

Seminal plasma accelerates semen-derived enhancer of viral infection (SEVI) fibril formation by the prostatic acid phosphatase (PAP248-286) peptide

Amyloid fibrils contained in semen, known as SEVI, or semen-derived enhancer of viral infection, have been shown to increase the infectivity of HIV dramatically. However, previous work with these fibrils has suggested that extensive time and nonphysiologic levels of agitation are necessary to induce amyloid formation from the precursor peptide (a proteolytic cleavage product of prostatic acid phosphatase, PAP(248-286)). Here, we show that fibril formation by PAP(248-286) is accelerated dramatically in the presence of seminal plasma (SP) and that agitation is not required for fibrillization in this setting. Analysis of the effects of specific SP components on fibril formation by PAP(248-286) revealed that this effect is primarily due to the anionic buffer components of SP (notably inorganic phosphate and sodium bicarbonate). Divalent cations present in SP had little effect on the kinetics of fibril formation, but physiologic levels of Zn(2+) strongly protected SEVI fibrils from degradation by seminal proteases. Taken together, these data suggest that in the in vivo environment, PAP(248-286) is likely to form fibrils efficiently, thus providing an explanation for the presence of SEVI in human semen.