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- Virta, J, et al.
(författare)
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Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
- 2022
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 43:2, s. 3076-3076
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Konferensbidrag (refereegranskat)abstract
- BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain.PurposeTo characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model.MethodsCardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET.ResultsCompared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B).ConclusionsObese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work.Funding AcknowledgementType of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT
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| 2. |
- Norha, Jooa, et al.
(författare)
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Standing time and daily proportion of sedentary time are associated with pain-related disability in a one month accelerometer measurement in adults with overweight or obesity
- 2022
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Ingår i: Scandinavian Journal of Pain. - Berlin : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 22:2, s. 317-324
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Tidskriftsartikel (refereegranskat)abstract
- The association between the subjective experience of pain-related disability (PRD) and device-measured physical activity (PA) and sedentary behavior (SB) in overweight and obese adults is not well known. The aim of this study was to investigate the associations of pain markers with accelerometer-measured SB duration and different intensities of PA among physically inactive middle-aged adults with overweight or obesity. This cross-sectional analysis included 72 subjects (27 men) with mean age of 57.9 (SD 6.7) years and mean BMI of 31.6 (SD 4.1) kg/m2. SB and standing time (ST), breaks in sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were measured for four consecutive weeks (mean 25 days, SD 4) with a hip-worn triaxial accelerometer. Headache, musculoskeletal pain, back pain, and PRD were assessed by visual analog scales (VAS) and using the Oswestry disability index (ODI). RAND-36 questionnaire was applied to assess health-related quality of life. The associations were studied by linear models. ST was positively and SB proportion was negatively associated with PRD when adjusted for age, sex, BMI, accelerometry duration, MVPA, pain medication use, and general health perceptions assessed by RAND-36. No associations were found between ST and back pain. SB or different PA intensities were not associated with pain experience at specific sites. Longer daily ST, but not LPA or MVPA is associated with higher level of PRD. Correspondingly, higher proportion of SB is associated with lower level of PRD. This suggests that individuals with PRD prefer to stand, possibly to cope with pain. These results may highlight the importance of habitual standing behaviors in coping with experienced PRD in adults with overweight or obesity. © 2021 Walter de Gruyter GmbH, Berlin/Boston.
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