A paucity of data exists regarding sex differences in age‐related obesity and insulin resistance, particularly in the preclinical murine model. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. Aged (AG, 18 months old) male C57BL/6J mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103 ± 6818 vs. 64,005 ± 2031, P = 0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2 ± 1.9 vs. 30.0 ± 0.4 g, P < 0.0001), fat mass (18.7 ± 2.0 vs. 3.3 ± 0.4 g, P < 0.0001), body fat (43.0 ± 3.0 vs. 11.0 ± 1.5%, P < 0.0001) than YG males. In AG females, body mass (32.8 ± 1.6 vs. 26.3 ± 0.9 g, P = 0.02) was higher, but fat mass (13.3 ± 2.0 vs. 9.5 ± 1.3 g, P = 0.24) and body fat (37.8 ± 4.8 vs. 35.5 ± 3.8%, P = 0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2 ± 1.9 vs. 32.8 ± 1.6 g, P = 0.001) and fat mass (18.7 ± 2.0 vs. 13.3 ± 2.0 g, P = 0.04) compared to AG females; however, body fat (43.0 ± 3.0 vs. 37.8 ± 4.8%, P = 0.28) was similar. Six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reverse age‐related obesity in male mice. Surprisingly, obesity and insulin resistance appear to be reversed in the oldest of the old male mice (28 vs. 20 months). Our findings indicate that female mice, unlike males, are protected from age‐related obesity and insulin resistance.

Introduction:Obesity is a public health epidemic that is projected to grow in coming years. Observational data on the epidemiologic profile and immediate postoperative outcomes of obesity and morbid obesity after revision total knee arthroplasty (rTKA) are limited.Methods:Discharge data from the National Inpatient Sample was used to identify patients who underwent rTKA from 2006 to 2015. Patients were stratified into morbidly obese, obese, and not obese control cohorts. An analysis was performed to compare etiology of revision, demographic and medical comorbidity profiles, and immediate in-hospital economic and complication outcomes after rTKA.Results:An estimated 605,603 rTKAs were included in this analysis. Morbidly obese and obese patients were at significantly higher risk for any complication than not obese patients. Patients with obesity were associated with an increased risk of postoperative anemia but a lower risk of peripheral vascular disease and gastrointestinal, and hematoma/seroma complications compared with not obese patients. Patients with morbid obesity were associated with an increased risk of any, hematoma/seroma, wound dehiscence, postoperative infection, pulmonary embolism, and postoperative anemia complications and a lower risk of gastrointestinal complications when compared with not obese patients. Morbidly obese patients had a significantly longer length of stay than both obese and not obese patients, while no significant difference in length of stay was observed between obese and not obese patients.Discussion:Morbidly obese patients are at higher odds for worse postoperative medical and economic outcomes compared with those with obesity after rTKA. As the number of patients with obesity and morbid obesity continues to rise, these risk factors should be considered in preoperative discussions and perioperative protocol optimization.

In the United States, the prevalence of obesity is increasing (Hales, Carroll, Fryar, & Ogden, 2017) alongside the number of elderly individuals (He, Goodking, & Kowal, 2016). Both obesity and aging are independent risk factors for many chronic diseases, including type 2 diabetes (Barnes, 2011;

Introduction:The purpose of this study was to assess the impact of underweight status on in-hospital postoperative outcomes and complications after revision total joint arthroplasty (rTJA) of the hip and knee. Methods: Data from the National Inpatient Sample were used to identify all patients undergoing rTJA in the United States between 2006 and 2015. Patients were divided into two groups based on a concomitant diagnosis of underweight body mass index and a control normal weight group. Propensity score analysis was performed to determine whether underweight body mass index was a risk factor for in-hospital postoperative complications and resource utilization. Results: A total of 865,993 rTJAs were analyzed. Within the study cohort, 2,272 patients were classified as underweight, whereas 863,721 were classified as a normal weight control group. Underweight patients had significantly higher rates of several comorbidities compared with the control cohort. Underweight patients had significantly higher rates of any complication (49.98% versus 33.68%, P = 0.0004) than normal weight patients. Underweight patients also had significantly greater length of stay compared with normal weight patients (6.50 versus 4.87 days, P , 0.0001). Conclusion: Underweight patients have notably higher rates of any complication and longer length of stay after rTJA than those who are not underweight. These results have important implications in preoperative patient discussions and perioperative management. Standardized preoperative protocols should be developed and instituted to improve outcomes in this patient cohort.T otal hip arthroplasty (THA) and total knee arthroplasty (TKA) have greatly improved the quality of life among patients with degenerative joint disease. 1,2 Despite the success of primary procedures, revision TKA (rTKA) and THA (rTHA) remain necessary in response to infections,

Introduction: There remain limited data on the effect of obesity on in-hospital outcomes after revision total hip arthroplasty (rTHA). Methods: Discharge data from the National Inpatient Sample were used to identify patients undergoing rTHA from 2006 to 2015. Propensity score analysis was done to analyze the effects of obesity and morbid obesity on in-hospital economic and complication outcomes after rTHA. Results: The estimated 460,297 rTHAs were done during the study period. Obese patients were more likely to suffer from any complication than not obese patients (41.44% versus 39.41%, P = 0.0085), and morbidly obese patients were more likely to suffer from any complication than obese patients (47.22% versus 41.44%, P , 0.0001). Obesity was associated with increased risk of postoperative anemia compared with not obese patients, while morbid obesity was associated with increased risk of postoperative anemia, hematoma/seroma, wound dehiscence, and postoperative infection (P , 0.05). Morbidly obese patients also had a significantly greater average length of stay (6.40 days) than obese (5.23 days) and not obese (5.37 days) patients (P , 0.0001). Discussion: Although both obesity and morbid obesity are associated with higher risk of in-hospital postoperative complications after rTHA, morbid obesity is a larger risk factor and is associated with a longer length of stay.A lthough primary total hip arthroplasty (THA) has a well-reported track record of excellent outcomes, the number of patients requiring revision THA (rTHA) for reasons such as implant failure, metallosis, infection, and instability has steadily increased in recent decades. 1 In 2014, a total of 50,220 rTHAs were done, and the incidence of the procedure is

A paucity of data exists regarding sex‐differences in age‐related obesity and insulin resistance. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. In aged (AG, 18 months old) male mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103±6,818 vs 64,005±2,031, P=0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2±1.9 vs 30.0±0.4 g, P<0.0001), fat mass (18.7±2.0 vs 3.3±0.4 g, P<0.0001), body fat (43.0±3.0 vs 11.0±1.5%, P<0.0001) than YG males. In AG females, body mass (32.8±1.6 vs 26.3±0.9 g, P=0.02) was higher, but fat mass (13.3±2.0 vs 9.5±1.3 g, P=0.24) and body fat (37.8±4.8 vs 35.5±3.8%, P=0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2±1.9 vs 32.8±1.6 g, P=0.001) and fat mass (18.7±2.0 vs 13.3±2.0 g, P=0.04) compared to AG females; however, body fat (43.0±3.0 vs 37.8±4.8%, P=0.28) was similar. Although aging and obesity are associated with higher levels of oxidative stress, six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reduce adiposity in AG male mice. Surprisingly, when AG male mice survive to 28 months of age, the obesity and insulin resistance that was observed at 18 months of age is reversed. In conclusion, our findings indicate that male mice, but not female mice, develop age‐related obesity and insulin resistance, a process that is reversed in the oldest of old mice.Support or Funding InformationNIA 1R15AG053790‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Age and obesity are risk factors for many chronic diseases, which are linked to inflammation and oxidative stress, and is thought to alter telomere function. Telomeres are the endcaps of eukaryotic chromosomes that maintain chromosomal structural integrity protecting genetic information. Telomeres are regulated and protected by the shelterin complex, made up of Telomere‐repeat binding factor 1 (TRF1) and 2 (TRF2), protection of telomeres 1 (POT1a and b) as well as the enzyme telomerase that can elongate telomeres. However, to date, the effect of a high‐fat diet and age on the shelterin complex of telomeres in adipose tissue has not been examined. Thus, the present study investigated the effects of a high‐fat diet and aging on C57Bl6J (N=15) mice adipose tissue mRNA expression of genes involved in the regulation of telomeres. Young mice were randomly assigned to be fed either a high‐fat (YG+HF; n=5; 60% kcal from fat) or a low fat diet (YG+LF; n=4; 10% kcal from fat) for three months. A subset of mice were fed a low fat diet (AGED; n=6; 10% kcal from fat) and aged until 16 months.RESULTSBody weight and epididymal white adipose tissue weight (EWAT) increased with age or a high‐fat diet. TRF1 mRNA expression was reduced by age and a high‐fat diet, whereas age alone reduced TRF2. mTERT, the gene that codes for the catalytic subunit of the enzyme telomerase, was significantly higher in the YG+HF than the YG+LF and AGED mice (p=0.001). Body weight was significantly correlated with TRF1 and TRF2 mRNA expression (p=0.01), whereas mTERT expression was significantly correlated to EWAT weight (p=0.008). There were no significant differences between groups for mRNA expression of POT1A (p=0.928) and POT1B (p=0.930), respectively. To understand potential impacts of alterations to shelterin complex proteins on phenotype we probed for tumor necrosis factor α (TNFα) and monocyte chemoattractant protein 1 (MCP1), though unexpectedly, mRNA expression in adipose tissue were significantly elevated in the YG+LF group compared to the YG+HF and aged groups for TNFα (p=0.001) and MCP1 (p=0.000), respectively. We also assessed gene expression of the tumor suppressor protein p53, which is involved in the DNA damage response. There was no significant difference between groups for p53 mRNA expression (p=0.199). A high‐fat diet, increased the expression of mTERT, the catalytic subunit of the enzyme telomerase, but decreased TRF1, whereas age decreased mTERT, TRF1, and TRF2. POT1a, POT1b, p53 were not different. Together, these findings suggest diet and age impact expression of the shelterin complex, and perhaps telomere function in adipose tissue which might be associated with the development of chronic disease associated with obesity or aging, but further work is needed.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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