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- Bariatric surgery can result in substantial weight loss and significant metabolic improvements. Therefore, clinicians should be prepared to taper treatments for chronic metabolic diseases. For patien...
Bariatric surgery can result in substantial weight loss and significant metabolic improvements. Therefore, clinicians should be prepared to taper treatments for chronic metabolic diseases. For patients with type 2 diabetes, early and dramatic improvements in glucose homeostasis require anticipatory management. This includes insulin dose reductions, discontinuation of certain oral agents, and close monitoring. Antihypertensive medications should be adjusted to avoid hypotension. Even after postoperative improvements in dyslipidemia, some patients will continue to meet criteria for statin therapy. While many obesity-related diseases will improve, clinicians should also be prepared to manage postoperative medical and nutritional complications. Micronutrient deficiencies are common, and professional guidelines provide recommendations for preoperative screening, universal postoperative supplementation, micronutrient monitoring, and repletion strategies. Changes in gastrointestinal physiology may result in dumping syndrome, and patients may report early gastrointestinal and vasomotor symptoms after eating. In contrast, post-gastric bypass hypoglycemia is a rare complication of malabsorptive procedures, resulting in insulin-mediated hypoglycemia after carbohydrate-containing meals. Rapid weight loss may increase the risk of cholelithiasis, which can be mitigated by ursodiol. After malabsorptive procedures, enteric hyperoxaluria and other factors may result in nephrolithiasis, which can be addressed with hydration, dietary interventions, and calcium. All bariatric surgeries induce a high bone turnover state, with declining bone mineral density (BMD) and increased fracture risk. Appropriate strategies include adequate calcium and vitamin D supplementation and age-appropriate BMD screening. In summary, given dramatic physiologic changes with bariatric surgery, clinicians should be prepared to taper treatments for chronic metabolic diseases, and to manage postoperative medical and nutritional complications. For complete coverage of this and all related areas of Endocrinology, please visit our FREE on-line web-textbook, www.endotext.org.
- Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance. [Journal Article]
- CRCell Rep 2018 Feb 20; 22(8):2133-2145
- While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as ...
While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33-/-mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33-/-mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33-/-mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.
- Unveiling network-based functional features through integration of gene expression into protein networks. [Review]
- BBBiochim Biophys Acta 2018 Feb 18
- Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might ...
Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might not be adequate to capture the complexity of phenotypes. Therefore, integrated multi-omics approaches have been used to unravel genotype-phenotype relationships such as global regulatory mechanisms and complex metabolic networks in different eukaryotic organisms. Some of the progress and challenges associated with integrated omics studies have been reviewed previously in comprehensive studies. In this work, we highlight and review the progress, challenges and advantages associated with emerging approaches, integrating gene expression and protein-protein interaction networks to unravel network-based functional features. This includes identifying disease related genes, gene prioritization, clustering protein interactions, developing the modules, extract active subnetworks and static protein complexes or dynamic/temporal protein complexes. We also discuss how these approaches contribute to our understanding of the biology of complex traits and diseases. This article is part of a Special Issue entitled: Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.
- Lipid Pathway Deregulation in Advanced Prostate Cancer. [Review]
- PRPharmacol Res 2018 Feb 18
- The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and...
The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1. Recently, there is growing evidence implicating the role of obesity and peri-prostatic adipose tissue (PPAT) in PC aggressiveness and related mortality, suggesting the importance of lipid pathways in both localised and disseminated disease. A number of promising agents are in development to target the lipogenic axis in PC, and the likelihood is that these agents will form part of combination drug strategies, with targeting of multiple metabolic pathways (e.g. FASN and CPT1), or in combination with AR pathway inhibitors (SCD1 and AR).
- Secretome Analysis of Hypoxia-Induced 3T3-L1 Adipocytes Uncovers Novel Proteins Potentially Involved in Obesity. [Journal Article]
- PProteomics 2018 Feb 21
- In the obese state, as adipose tissue expands, adipocytes become hypoxic and dysfunctional, leading to changes in the pattern of adipocyte-secreted proteins. To better understand the role of hypoxia ...
In the obese state, as adipose tissue expands, adipocytes become hypoxic and dysfunctional, leading to changes in the pattern of adipocyte-secreted proteins. To better understand the role of hypoxia in the mechanisms linked to obesity, we comparatively analyzed the secretome of murine differentiated 3T3-L1 adipocytes exposed to normoxia or hypoxia for 24 h. Proteins secreted into the culture media were precipitated by trichloroacetic acid and then digested with trypsin. The peptides were labeled with dimethyl labeling and analyzed by reversed phase nanoscale liquid chromatography coupled to a quadrupole Orbitrap mass spectrometer. From a total of 1508 identified proteins, 109 were differentially regulated, of which 108 were genuinely secreted. Factors significantly downregulated in hypoxic conditions included adiponectin, a known adipokine implicated in metabolic processes, as well as thrombospondin-1 and -2, and matrix metalloproteinase-11, all multifunctional proteins involved in extracellular matrix (ECM) homeostasis. Findings were validated by Western blot analysis. Expression studies of the relative genes were performed in parallel experiments in vitro, in differentiated 3T3-L1 adipocytes, and in vivo, in fat tissues from obese vs lean mice. Our observations are compatible with the concept that hypoxia may be an early trigger for both adipose cell dysfunction and ECM remodeling. This article is protected by copyright. All rights reserved.
- Synthesis and Characterization of the R27S Genetic Variant of Insulin-like Peptide 5. [Journal Article]
- CChemMedChem 2018 Feb 21
- We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analog that was recently discovered as a genetic mutation in an Amish population. The mutation was as...
We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analog that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analog to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP-4), suggesting an alternative basis for the observed effect. In preparation of this synthetically challenging hormone, we have introduced several improvements such as implementation of isoacyl chemistry for high-efficiency preparation of INSL5 B-chain and selective intramolecular A6-11 disulfide formation as a first step in sequential disulfide assembly.
- Association of Hidradenitis Suppurativa With Body Image. [Journal Article]
- JDJAMA Dermatol 2018 Feb 21
- CONCLUSIONS: Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.
- [Infoxication in health. Health information overload on the Internet and the risk of important information becoming invisible]. [Journal Article]
- RPRev Panam Salud Publica 2018 Feb 19; 41:e115
- CONCLUSIONS: We conclude that public health would benefit from: health institutions implementing formal knowledge management strategies; academic health sciences institutions incorporating formal digital literacy programs; and having health workers who are professionally responsible and functional in the information society.
- Sports Practices and Cardiovascular Risk in Teenagers. [Journal Article]
- ABArq Bras Cardiol 2018 Feb 19
- CONCLUSIONS: High prevalence of hypertension, overweight/obesity and altered blood lipid profile was found in this group of adolescents. Regular sports training program combined with little influence of their eating habits outside school may contribute to a better metabolic profile and reduction in cardiovascular risk factors in students. Public health measures are also need.
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- Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach. [Journal Article]
- PlosPLoS One 2018; 13(2):e0193138
- CONCLUSIONS: Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.