Porcine growth hormone: a central metabolic hormone involved in the regulation of adipose tissue growth.

During the past 20 y, much has been learned about how porcine growth hormone (pGH) affects growth and nutrient partitioning in growing pigs. Our contemporary understanding of the biology of pGH has as its roots the seminal studies conducted by Larry Machlin. His studies and many subsequent reports by other investigators have established that treatment of growing pigs with pGH markedly stimulates muscle growth and, concurrently, reduces fat deposition. In growing pigs, maximally effective doses of pGH increase average daily gain as much as 10% to 20%, improve feed efficiency 15% to 30%, decrease adipose tissue mass and lipid accretion rates by as much as 50% to 80%, and concurrently increase protein deposition by 50%. These effects are associated with a decrease in feed intake of approximately 10% to 15%. These responses occur because pGH has a wide array of biological effects that modulate nutrient partitioning between adipose tissue and skeletal muscle. The decrease in adipose tissue growth is due to a reduction in lipogenesis that is the consequence of pGH blunting the effects of many insulin-dependent events. This article provides an overview of some of the biological effects pGH has in adipose tissue and discusses what is known about the underlying mechanisms that account for these effects.     

Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells

The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein.     

Low fat and high monounsaturated fat diets decrease human low density lipoprotein oxidative susceptibility in vitro

Oxidative modification of low density lipoprotein (LDL) is thought to play an important role in the development of atherosclerosis. Some studies have found that LDL enriched in monounsaturated fatty acids (MUFA) are less susceptible to oxidation than LDL enriched in polyunsaturated fatty acids (PUFA). A high MUFA diet is an alternative to a lower-fat blood cholesterol-lowering diet. Less is known about the effects of high MUFA versus lower-fat blood cholesterol-lowering diets on LDL oxidative susceptibility. The present study was designed to evaluate the effects of men and women consuming diets high in MUFA (peanuts plus peanut butter, peanut oil and olive oil) on LDL oxidative susceptibility, and to compare these effects with those of a Step II blood cholesterol-lowering diet. A randomized, double-blind, five-period crossover design (n = 20) was used to study the effects of the following diets on LDL-oxidation: average American [35% fat, 15% saturated fatty acids (SFA)], Step II (25% fat, 7% SFA), olive oil (35% fat, 7% SFA), peanut oil (35% fat, 7% SFA) and peanuts plus peanut butter (35% fat, 8% SFA). The average American diet resulted in the shortest lag time (57 +/- 6 min) for LDL oxidized ex vivo, whereas the Step II, olive oil and peanuts plus peanut butter diets resulted in a lag time of 66 +/- 6 min (P < or = 0.1). The slower rate of oxidation [nmol dienes/(min x mg LDL protein)] observed when subjects consumed the olive oil diet (24 +/- 2) versus the average American (28 +/- 2), peanut oil (28 +/- 2) and peanuts plus peanut butter diets (29 +/- 2; P < or = 0.05) was associated with a lower LDL PUFA content. The results of this study suggest that lower-fat and higher-fat blood cholesterol-lowering diets high in MUFA have similar effects on LDL oxidative resistance. In addition, our results suggest that different high MUFA sources varying in the ratio of MUFA to PUFA can be incorporated into a high MUFA diet without increasing the susceptibility of LDL to oxidation.     

Detecting Malingered Pain-Related Disability: Classification Accuracy of the Test of Memory Malingering

This study used criterion groups validation to determine the accuracy of the Test of Memory Malingering (TOMM) in detecting malingered pain-related disability (MPRD) across a range of cutoffs in chronic pain patients undergoing psychological evaluation (n = 604). Data from patients with traumatic brain injury (n = 45) and dementia (n = 59) are presented for comparison. TOMM scores decreased and failure rates increased as a function of greater external evidence of intentional under-performance. The TOMM detected from 37.5% to 60.2% of MPRD patients, depending on the cutoff. False positive (FP) error rates ranged from 0% to 5.1%. Accuracy data for Trial 1 are also reported. In chronic pain the original cutoffs produced no FP errors but were associated with high false negative error rates. Higher cutoffs increased sensitivity without adversely affecting specificity. The relevance of these findings to research and clinical practice is discussed.     

Detecting Malingered Pain-Related Disability: Classification Accuracy of the Portland Digit Recognition Test

This study used criterion groups validation to determine the classification accuracy of the Portland Digit Recognition Test (PDRT) at a range of cutting scores in chronic pain patients undergoing psychological evaluation ( n = 318), college student simulators ( n = 29), and patients with brain damage ( n = 120). PDRT scores decreased and failure rates increased as a function of greater independent evidence of intentional underperformance. There were no differences between patients classified as malingering and college student simulators. The PDRT detected from 33% to nearly 60% of malingering chronic pain patients, depending on the cutoff used. False positive error rates ranged from 3% to 6%. Scores higher than the original cutoffs may be interpreted as indicating negative response bias in patients with pain, increasing the usefulness and facilitating the clinical application of the PDRT in the detection of malingering in pain.     

Effective Reserve: A Latent Variable to Improve Outcome Prediction in Stroke

Prediction of functional outcome after stroke based on initial presentation remains an open challenge, suggesting that an important aspect is missing from these prediction models. There exists the notion of a protective mechanism called brain reserve, which may be utilized to understand variations in disease outcome. In this work, we expand the concept of brain reserve (effective reserve) to improve prediction models of functional outcome after acute ischemic stroke (AIS). Consecutive AIS patients with acute brain magnetic resonance imaging (<48 hours) were eligible for this study. White matter hyperintensity and acute infarct volume were determined on T2 fluid attenuated inversion recovery and diffusion weighted images, respectively. Modified Rankin Scale scores were obtained at 90days poststroke. Effective reserve was defined as a latent variable using structural equation modeling by including age, systolic blood pressure, and intracranial volume measurements. Of 453 AIS patients (mean age 66.6 ± 14.7 years), 36% were male and 311 hypertensive. There was inverse association between effective reserve and 90-day modified Rankin Scale scores (path coefficient ?0.18 ± 0.01, P < .01). Compared to a model without effective reserve, correlation between predicted and observed modified Rankin Scale scores improved in the effective-reserve-based model (Spearman's ρ 0.29 ± 0.18 versus 0.15 ± 0.17, P < .001). Furthermore, hypertensive patients exhibited lower effective reserve (P < 10^?6). Using effective reserve in prediction models of stroke outcome is feasible and leads to better model performance. Furthermore, higher effective reserve is associated with more favorable functional poststoke outcome and might correspond to an overall better vascular health.