Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue

Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n = 7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n = 10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA

Prediction of Suicide and Nonfatal Self-harm After Bariatric Surgery: A Risk Score Based on Sociodemographic Factors, Lifestyle Behavior, and Mental Health : A Nonrandomized Controlled Trial

Objective: To identify preoperative sociodemographic and health-related factors that predict higher risk of nonfatal self-harm and suicide after bariatric surgery. Background: Evidence is emerging that bariatric surgery is related to an increased risk of suicide and self-harm, but knowledge on whether certain preoperative characteristics further enhance the excess risk is scarce. Methods: The nonrandomized, prospective, controlled Swedish Obese Subjects study was linked to 2 Nationwide Swedish registers. The bariatric surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual care. Participants were recruited from 1987 to 2001, and information on the outcome (a death by suicide or nonfatal self-harm event) was retrieved until the end of 2016. Subhazard ratios (sub-HR) were calculated using competing risk regression analysis. Results: The risk for self-harm/suicide was almost twice as high in surgical patients compared to control patients both before and after adjusting for various baseline factors [adjusted sub-HR = 1.98, 95% confidence interval (CI) = 1.34-2.93]. Male sex, previous healthcare visits for self-harm or mental disorders, psychiatric drug use, and sleep difficulties predicted higher risk of self-harm/suicide in the multivariate models conducted in the surgery group. Interaction tests further indicated that the excess risk for self-harm/suicide related to bariatric surgery was stronger in men (sub-HR = 3.31, 95% CI = 1.73-6.31) than in women (sub-HR = 1.54, 95% CI = 1.02-2.32) (P = 0.007 for adjusted interaction). A simple-to-use score was developed to identify those at highest risk of these events in the surgery group. Conclusions: Our findings suggest that male sex, psychiatric disorder history, and sleep difficulties are important predictors for nonfatal self-harm and suicide in postbariatric patients. High-risk patients who undergo surgery might require regular postoperative psychosocial monitoring to reduce the risk for future self-harm behaviors.Peer reviewe

No Evidence for a Role of Adipose Tissue-Derived Serum Amyloid A in the Development of Insulin Resistance or Obesity-Related Inflammation in hSAA1^+/− Transgenic Mice

<div><p>Obesity is associated with a low-grade inflammation including moderately increased serum levels of the acute phase protein serum amyloid A (SAA). In obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are associated with insulin resistance. SAA has been described as a chemoattractant for inflammatory cells and adipose tissue from obese individuals contains increased numbers of macrophages. However, whether adipose tissue-derived SAA can have a direct impact on macrophage infiltration in adipose tissue or the development of insulin resistance is unknown. The aim of this study was to investigate the effects of adipose tissue-derived SAA1 on the development of insulin resistance and obesity-related inflammation. We have previously established a transgenic mouse model expressing human SAA1 in the adipose tissue. For this report, hSAA1^+/− transgenic mice and wild type mice were fed with a high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were assessed using an oral glucose tolerance test. Real-time PCR was used to measure the mRNA levels of macrophage markers and genes related to insulin sensitivity in adipose tissue. Cytokines during inflammation were analyzed using a Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease in mRNA levels of genes related to insulin sensitivity in adipose tissue in neither male nor female hSAA1 animals. Furthermore, serum levels of proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue were not increased in hSAA1 mice. Hence, in this model we find no evidence that adipose tissue-derived hSAA1 influences the development of insulin resistance or obesity-related inflammation.</p></div

Perceived Body Size in Relation to 10-Year Weight Change in the Swedish Obese Subjects Intervention Study

Introduction: Body size underestimation in patients with obesity may be associated with long-term weight increase. In the current report, we analyse changes in body size perception in patients with obesity undergoing either bariatric surgery or usual obesity care, and in subgroups of patients who gain weight or maintain their body weight over 10 years. Materials and Methods: A total of 2,504 patients with obesity from the prospective, controlled Swedish Obese Subjects (SOS) intervention study were included in this report, 1,370 patients underwent bariatric surgery and 1,134 patients were usual care controls. Weight was measured and body size was self-estimated using the Stunkard’s figure rating scale at baseline and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years of follow-up. A body perception index (BPI) was calculated as estimated/measured BMI. Weight (re)gain was defined as ≥10% increase between 1 and 10 years of follow-up. Results: Body size was underestimated by 12% in the surgery and 14% in the control group (i.e., &gt;5 BMI units) at baseline and underestimation largely persisted over 10 years in both intervention groups. When stratified by long-term weight development, weight regainers from the surgery group underestimated their body size to a larger degree compared to weight maintainers (12 vs. 9%, p &lt; 0.001) after 10 years. Likewise weight gainers in the control group also underestimated their body size to a larger degree (17% vs. 13%, p &lt; 0.001). In both groups, the change in BPI was significantly different between weight regainers and maintainers during follow-up (time-BPI interactions both p &lt; 0.001). Conclusion: Patients with obesity underestimate their body size and this underestimation remains long-term even after major weight loss induced by bariatric surgery. In patients with obesity who maintain their weight, regardless of treatment, underestimation of body size persists but body size perception is slightly more accurate compared to patients who gain or regain weight long-term

Adipose tissue mRNA levels of macrophage markers.

<p>mRNA levels of macrophage markers in (A) the gonadal fat depot and (B) the retroperitoneal fat depot in male mice. n = 8–10 per group. *indicates p<0.05, **p<0.01 and ***p<0.001.</p

Adipose tissue mRNA levels of genes related to insulin sensitivity.

<p>mRNA levels of insulin sensitivity-related genes in (A) the gonadal fat depot and (B) the retroperitoneal fat depot in male mice. n = 8–10 per group. *indicates p<0.05, **p<0.01 and ***p<0.001.</p

Animal growth curves.

<p>Growth curves for male hSAA1 mice (filled squares) and wt mice (open circles) fed either with a HFD (solid line) or NC (dashed line) for 12 weeks. n = 8–10 per group.</p

Inflammatory markers in plasma.

<p>Levels of inflammatory markers in plasma (pg/ml) in male mice fed with HFD. n = 9–10 per group.</p>*<p>indicates p<0.05.</p