INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G\u3eC, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035). Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation

Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE), might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise) or late recovery (24 h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n = 6) and women (n = 8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.</p> <p>Results</p> <p>This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females. Sex differences in skeletal muscle transcriptional regulation might implicate a mechanism behind disproportional muscle growth in males as compared with female counterparts after RE training at the same relative intensity.</p> <p>Conclusions</p> <p>Sex differences exist in skeletal muscle gene transcription both at rest and following acute RE, suggesting that sex is a significant modifier of the transcriptional regulation in skeletal muscle. The findings from the present study provide insight into the molecular mechanisms for sex differences in muscle phenotypes and for muscle transcriptional regulation associated with training adaptations to resistance exercise.</p

Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies

A set of software tools for building and distributing models of macromolecular assemblies uses an integrative structure modeling approach, which casts the building of models as a computational optimization problem where information is encoded into a scoring function used to evaluate candidate models

Evolving concepts on the age-related changes in “muscle quality”

The deterioration of skeletal muscle with advancing age has long been anecdotally recognized and has been of scientific interest for more than 150 years. Over the past several decades, the scientific and medical communities have recognized that skeletal muscle dysfunction (e.g., muscle weakness, poor muscle coordination, etc.) is a debilitating and life-threatening condition in the elderly. For example, the age-associated loss of muscle strength is highly associated with both mortality and physical disability. It is well-accepted that voluntary muscle force production is not solely dependent upon muscle size, but rather results from a combination of neurologic and skeletal muscle factors, and that biologic properties of both of these systems are altered with aging. Accordingly, numerous scientists and clinicians have used the term “muscle quality” to describe the relationship between voluntary muscle strength and muscle size. In this review article, we discuss the age-associated changes in the neuromuscular system—starting at the level of the brain and proceeding down to the subcellular level of individual muscle fibers—that are potentially influential in the etiology of dynapenia (age-related loss of muscle strength and power)

multicenter study from Turkey

Purpose: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the secondor third-line setting.Methods: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a secondor third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included.Results: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (p(PFS)=0.22 and p(OS)=0.85).Conclusion: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.C1 [Hacioglu, Muhammet Bekir; Kostek, Osman; Erdogan, Bulent; Cicin, Irfan] Trakya Univ, Dept Med Oncol, Med Fac, Edirne, Turkey.[Karabulut, Senem; Tastekin, Didem] Istanbul Univ, Med Fac, Dept Med Oncol, Istanbul, Turkey.[Goksu, Sema Sezgin] Akdeniz Univ, Med Fac, Dept Med Oncol, Antalya, Turkey.[Alandag, Celal] Karadeniz Tech Univ, Med Fac, Dept Med Oncol, Trabzon, Turkey.[Akagunduz, Baran] Dokuz Eylul Univ, Med Fac, Dept Med Oncol, Izmir, Turkey.[Bilgetekin, Irem] Dr Abdurrahman Yurtaslan Ankara Oncol Training &, Dept Med Oncol, Ankara, Turkey.[Caner, Burcu; Sahin, Ahmet Bilgehan] Uludag Univ, Med Fac, Dept Med Oncol, Bursa, Turkey.[Yildiz, Birol] Gulhane Training & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Kose, Fatih] Baskent Univ, Adana Med Fac, Dept Med Oncol, Adana, Turkey.[Kaplan, Muhammet Ali] Dicle Univ, Med Fac, Dept Med Oncol, Diyarbakir, Turkey.[Gulmez, Ahmet] Inonu Univ, Med Fac, Dept Med Oncol, Malatya, Turkey.[Dogan, Ender] Erciyes Univ, Med Fac, Dept Med Oncol, Kayseri, Turkey.[Kilickap, Saadettin] Hacettepe Univ, Med Fac, Dept Med Oncol, Ankara, Turkey.[Guven, Deniz Can; Gurbuz, Mustafa] Ankara Univ, Med Fac, Dept Med Oncol, Ankara, Turkey.[Ergun, Yakup] Ankara Numune Training & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Karaagac, Mustafa] Necmettin Erbakan Univ, Med Fac, Dept Med Oncol, Konya, Turkey.[Demiray, Atike Gokcen] Pamukkale Univ, Med Fac, Dept Med Oncol, Denizli, Turkey.[Turker, Sema] DiskapiYildir Beyazit Training & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Sakalar, Teoman] Sakarya Univ Training & Res Hosp, Dept Med Oncol, Aksaray, Turkey.[Ozkul, Ozlem] Sakarya Univ Training & Res Hosp, Dept Med Oncol, Sakarya, Turkey.[Telli, Tugba Akin] Marmara Univ, Med Fac, Dept Med Oncol, Istanbul, Turkey.[Sahin, Suleyman] Van Training & Res Hosp, Dept Med Oncol, Van, Turkey.[Bilici, Ahmet] Medipol Univ, Med Fac, Dept Med Oncol, Istanbul, Turkey