Growth hormone secretagogue receptor-1a mediates ghrelin's effects on attenuating tumour-induced loss of muscle strength but not muscle mass.

BACKGROUND: Ghrelin may ameliorate cancer cachexia (CC) by preventing anorexia, muscle, and fat loss. However, the mechanisms mediating these effects are not fully understood. This study characterizes the pathways involved in muscle mass and strength loss in the Lewis lung carcinoma (LLC)-induced cachexia model, and the effects of ghrelin in mice with or without its only known receptor: the growth hormone secretagogue receptor-1a ((GHSR-1a), Ghsr+/+ and Ghsr-/- ). METHODS: Five to 7-month-old male C57BL/6J Ghsr+/+ and Ghsr-/- mice were inoculated with 1 × 106 heat-killed (HK) or live LLC cells (tumour implantation, TI). When tumours were palpable (7 days after TI), tumour-bearing mice were injected with vehicle (T + V) or ghrelin twice/day for 14 days (T + G, 0.8 mg/kg), while HK-treated mice were given vehicle (HK + V). Body weight and grip strength were evaluated before TI and at termination (21 days after TI). Hindlimb muscles were collected for analysis. RESULTS: Less pronounced body weight (BW) loss (87.70 ± 0.98% vs. 83.92 ± 1.23%, percentage of baseline BW in tumour-bearing Ghsr+/+ vs. Ghsr-/- , P = 0.008), and lower upregulation of ubiquitin-proteasome system (UPS, MuRF1/Trim63, 5.71 ± 1.53-fold vs. 9.22 ± 1.94-fold-change from Ghsr+/+ HK + V in tumour-bearing Ghsr+/+ vs. Ghsr-/- , P = 0.036) and autophagy markers (Becn1, Atg5, Atg7, tumour-bearing Ghsr+/+  < Ghsr-/- , all P < 0.02) were found in T + V Ghsr+/+ vs. Ghsr-/- mice. Ghrelin attenuated LLC-induced UPS marker upregulation in both genotypes, [Trim63 was decreased from 5.71 ± 1.53-fold to 1.96 ± 0.47-fold in Ghsr+/+ (T + V vs. T + G: P = 0.032) and 9.22 ± 1.94-fold to 4.72 ± 1.06-fold in Ghsr-/- (T + V vs. T + G: P = 0.008)]. Only in Ghsr+/+ mice ghrelin ameliorated LLC-induced grip strength loss [improved from 89.24 ± 3.48% to 97.80 ± 2.31% of baseline (T + V vs. T + G: P = 0.042)], mitophagy markers [Bnip3 was decreased from 2.28 ± 0.56 to 1.38 ± 0.14-fold (T + V vs. T + G: P ≤ 0.05)], and impaired mitochondrial respiration [State 3u improved from 698.23 ± 73.96 to 934.37 ± 95.21 pmol/min (T + V vs. T + G: P ≤ 0.05)], whereas these markers were not improved by ghrelin Ghsr-/- . Compared with Ghsr+/+ , Ghsr-/- tumour-bearing mice also showed decreased response to ghrelin in BW [T + G-treated Ghsr+/+ vs. Ghsr -/- : 91.75 ± 1.05% vs. 86.18 ± 1.13% of baseline BW, P < 0.001)], gastrocnemius (T + G-treated Ghsr+/+ vs. Ghsr-/- : 96.9 ± 2.08% vs. 88.15 ± 1.78% of Ghsr+/+ HK + V, P < 0.001) and quadriceps muscle mass (T + G-treated Ghsr+/+ vs. Ghsr-/- : 96.12 ± 2.31% vs. 88.36 ± 1.94% of Ghsr+/+ HK + V, P = 0.01), and gastrocnemius type IIA (T + G-treated Ghsr+/+ vs. Ghsr-/- : 1250.49 ± 31.72 vs. 1017.62 ± 70.99 µm2 , P = 0.027) and IIB fibre cross-sectional area (T + G-treated Ghsr+/+ vs. Ghsr-/- : 2496.48 ± 116.88 vs. 2183.04 ± 103.43 µm2 , P = 0.024). CONCLUSIONS: Growth hormone secretagogue receptor-1a mediates ghrelin's effects on attenuating LLC-induced weakness but not muscle mass loss by modulating the autophagy-lysosome pathway, mitophagy, and mitochondrial respiration.

Impact of Common Food Labels on Consumer Liking in Vanilla Yogurt.

As competition on super market shelves is higher than ever, the importance of product concepts, communicated through labels, can dictate a product's success or failure. However, it is possible for labels to affect a consumer's experience, changing the overall response to the product. In this study, we tested samples of vanilla yogurt with one of four commonly used labeling concepts (high-protein, low-fat, made with stevia and all-natural) on sensory perception, consumer liking, expected consumption amount, and willingness to pay (WTP) in a consumer test (n = 108). Each participant evaluated five samples of the same vanilla yogurt identified with one of the labels, or an unlabeled control. Results showed panelists liked the samples labeled with low-fat and high-protein to the greatest degree, with all-natural scoring the lowest. Those more concerned with protein content found the samples less satiating, dependent on sex. Sweetness was also perceived more highly in younger panelists, with panelists WTP dependent on their liking of the labels. Results highlight the importance of labeling as an extrinsic cue affecting liking ratings, with potential ramification for ultimate product success. Understanding consumers' response to labels, as well as their attitudes, has broad implications for food marketing, as well as public health and the study of eating habits.

Steroids in regional analgesia.

IMPORTANCE OF THE FIELD: Local injections of steroids have been widely practiced to provide regional analgesia for the treatment of a wide variety of musculoskeletal pain syndromes. However, evidence regarding the effectiveness of steroid injections is not substantial. Also, there have been reports of catastrophic complications associated with their use. AREAS COVERED IN THIS REVIEW: The evidence currently available in the literature (Database: Ovid MEDLINE 1950 to 2010) is reviewed. The areas covered include the analgesic mechanisms of steroids, indications for steroid injections and their effectiveness, as well as the risks and precautions for steroid injections. WHAT THE READER WILL GAIN: This is an up-to-date review on the clinical application of steroid injections for regional analgesia, which will give the reader an insight on how to maximize the benefits of steroids while minimizing their side effects and complications. TAKE HOME MESSAGE: Although steroid injections are generally considered effective and safe in the treatment of painful condition of limbs, their use in the treatment of chronic back pain is still controversial and serious complications have been reported. More studies on outcome and safety are warranted.