ECSS Paris 2023: OP-MH18
INTRODUCTION: Incretin-based therapies, including Tirzepatide (T, Mounjaro), have transformed the management of obesity. We hypothesised that resistance training, combined with tirzepatide treatment, would lead to greater improvements in cardiovascular risk factors than tirzepatide alone. METHODS: In this randomised controlled trial, 110 participants aged 50-70 years with a body mass index (BMI) of ≥30, or ≥27kg/m² with ≥1 comorbidity, received a once weekly dose of tirzepatide for 24 consecutive weeks (Tirzepatide & Resistance Exercise: T+REX, n=55, M=28, F=27; Tirzepatide & No Exercise: T+NEX, n=55 M=30 F=25). T+REX attended progressive, supervised, centre-based resistance exercise thrice weekly. Risk factors measured at Wk 0 and Wk 24 included body mass, BMI, waist circumference, waist:hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP) and resting heart rate (HR). Two-way repeated measures ANOVA was conducted to test for time and group*time interactions. RESULTS: After an average 24 weeks of treatment, body mass decreased by 16.6±10.8 (99.6±17.3 to 83.0±14.2 kg, P<0.001), BMI by 5.9±1.6 (33.8±3.8 to 27.9±3.9 kg/m2, P<0.001), waist circumference by 15.2±5.6 (108.6± 11.6 cm to 93.4±11.9 cm, P<0.001), WHR by 0.04±0.04 (0.9±0.1 to 0.8±0.1, P<0.001), SBP by 12±10 (129±14 to 117±12 mmHg, P<0.001) and DBP 5±7 (75±9 to 70±8 mmHg, P<0.001). No significant group*time interactions were evident for any of these variables. Resting HR increased over time by 5±7 (63±8 to 68±8 bpm, P<0.001), also with no significant group*time interaction. CONCLUSION: This is the first study to investigate the impacts of tirzepatide, with and without supervised resistance exercise, in overweight/obese individuals on a variety of metabolic health markers. Tirzepatide treatment resulted in improvements in all CV risk factors over 24 weeks of treatment, except for resting heart rate which increased. There was no interaction of resistance exercise with tirzepatide treatment on these outcomes. Engaging in resistance exercise may result in modest improvements in cardiovascular risk factors beyond those associated with tirzepatide treatment alone.
Read CV Evie WintertonECSS Paris 2023: OP-MH18
INTRODUCTION: Excessive intramyocellular lipid droplet (LD) storage and mitochondrial dysfunction may represent hallmarks of both ageing and obesity. Heterogeneity in lipid droplet morphology and positioning at the subcellular and single fibre level obscures whether obesity worsens age related declines in muscle ‘quality’. The exercise-induced motility of LDs and the associated structural and metabolic alterations in LD composition, size, and interactions with mitochondria and other organelles likely also underpin their capacity for substrate oxidation and association with impairments in metabolic health. Therefore, this study examined age- and obesity-related differences in intramyocellular LD organisation and LD-mitochondrial interactions at the single-fibre level at rest and following a bout of physical activity. METHODS: To assess age- and obesity-related differences in LD organisation and LD–mitochondrial interactions, quantitative transmission electron microscopy was used to analyse intramuscular LDs at the single-fibre level in muscle biopsy samples from 15 young non-obese (23 ± 4 years, Body mass index [BMI]; 24 ± 3 kg·m-2, Body fat: 13 ± 5%), 10 older non-obese (69 ± 5 years, BMI; 25 ± 2 kg·m-2, Body fat: 20 ± 3%) and 10 older obese (73 ± 5 years, BMI; 31 ± 3 kg·m-2, Body fat: 33 ± 3%). LD morphology, subcellular distribution, and LD-mitochondrial contacts were assessed at rest and immediately following the completion of a 45-min bout of brisk walking. Z-disc width was used to indicate muscle fiber type. RESULTS: Ageing was associated with greater total LD volume density, driven primarily by increased intermyofibrillar lipid accumulation. This effect was confined to type II fibres. In contrast, older obese individuals exhibited a compartment-specific increase in subsarcolemmal LD volume density, likely reflecting larger LD size rather than increased LD number, and potentially also showing a bias towards type II fibres. Brisk walking did not alter LD volume density in any subcellular compartment but did reduce IMF LD size across all groups. Absolute LD-mitochondrial contact decreased post-brisk walking but was maintained relative to LD size. CONCLUSION: In conclusion, ageing and obesity impose distinct yet converging disruptions to intramyocellular lipid architecture. Ageing seems to drive intermyofibrillar lipid accumulation, whereas obesity preferentially expands subsarcolemmal stores. These compartment specific alterations show minimal responsiveness to acute moderate intensity walking. Together, the findings identify subcellular lipid distribution and LD–mitochondrial coupling as mechanistic features that may underpin the accelerated age related decline in skeletal muscle metabolic health in older adults with obesity.
Read CV Paul T MorganECSS Paris 2023: OP-MH18
INTRODUCTION: GLP-1 receptor agonists, such as semaglutide, are widely used in obesity treatment as these drugs induce substantial weight loss, primarily through appetite suppression. A growing number of athletes are using these drugs to optimise body composition. However, there are concerns that semaglutide-associated weight loss may induce greater muscle wasting, compared with traditional dietary interventions. The aim of the study was to compare the effects of semaglutide and caloric restriction on body composition and skeletal muscle mass in obese mice. METHODS: High-fat diet (HFD) fed obese 8-month-old male C57BL/6J mice were assigned either to a semaglutide (SEMA) (n=39) or caloric restriction (CR) (n=41) group for 28-days. CR group was matched by energy intake to SEMA group. A group of obese mice (OB) (n=9) continued to be fed HFD ad libitum and served as controls. Body mass was recorded daily. Body composition was assessed using bioimpedance spectroscopy, and major adipose depots and hindlimb skeletal muscles were weighed after dissection post mortem. Data were analysed using a two-way repeated-measures ANOVA to assess the effects of intervention, time, and their interaction, followed by appropriate post hoc tests. RESULTS: SEMA and CR groups exhibited similar reductions in energy intake compared to OB group (-25.6 ± 7.3 and -25.7 ± 2.8 vs. 3.9 ± 7.6%, P < 0.001) and had lower body mass post intervention (38.6 ± 4.2 and 39.5 ± 3.1 vs 49.1 ± 4.9 g, P < 0.001). From day 11 onwards, % body mass loss was greater in the SEMA group than in the CR group and remained so until the end of the intervention, resulting in a greater total weight loss (-19.7 ± 4.6 vs. -16.6 ± 2.4% from initial, P < 0.001). Total body water and intracellular water were reduced in both intervention groups compared with their initial values, with a more pronounced decrease observed in the SEMA group (P < 0.05). Despite these differences, post-mortem analysis of isolated muscle weights revealed no evidence of greater skeletal muscle loss in the SEMA group compared to CR group. Composite muscle mass index in the SEMA group was similar to CR (414.1 ± 17.9 and 427.3± 15.0 mg, P > 0.05) but lower compared to the OB group (435.2 ± 15.1 mg, P < 0.05). Composite fat mass was markedly reduced in both the SEMA and CR groups compared with the OB group (5.17 ± 1.25 and 5.87 ± 0.61 vs. 7.73 ± 1.00 g, P < 0.01). CONCLUSION: Semaglutide induces greater weight loss than caloric restriction, even when energy intake is similar, with no differences in the loss of skeletal muscle mass. These findings suggest that concerns regarding excessive muscle wasting with semaglutide may be overstated.
Read CV Petras MinderisECSS Paris 2023: OP-MH18