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Background & Aims: It is unclear if dietary adjustments to maintain energy balance during reduced physical activity can offset inactivity-induced reductions in insulin sensitivity and glucose disposal to produce normal daily glucose concentrations and meal responses. Therefore, the aim of the present study was to examine the impact of long-term physical inactivity (60 days of bed rest) on daily glycemia when in energy balance. Methods: Interstitial glucose concentrations were measured using Continuous Glucose Monitoring Systems (CGMS) for 5 days before and towards the end of bed rest in 20 healthy, young males (Age: 34 ± 8 years; BMI: 23.5 ± 1.8 kg/m2). Energy intake was reduced during bed rest to match energy expenditure, but the types of foods and timing of meals was maintained. Fasting venous glucose and insulin concentrations were determined, as well as the change in whole-body glucose disposal using a hyperinsulinemic-euglycemic clamp (HIEC). Results: Following long-term bed rest, fasting plasma insulin concentration increased 40% (p=0.004) and glucose disposal during the HIEC clamp decreased 24% (p

Key points Ageing is associated with increased systemic inflammation and metabolic dysfunction that contributes to the development of age-associated diseases. The role of adipose tissue in immunometabolic alterations that take place with ageing is unknown in humans. We show, in healthy, active and lean older adults, that adipose tissue, but not skeletal muscle, displays considerable pro-inflammatory transcriptomic, cellular and secretory changes, as well as a reduction in insulin signalling proteins compared to younger adults. These findings indicate that adipose tissue undergoes substantial immunometabolic alterations with ageing, and that these changes are tissue-specific and more profound than those observed in skeletal muscle or in the circulation. These results identify adipose tissue as an important tissue in the biological ageing process in humans, which may exhibit signs of immunometabolic dysfunction prior to systemic manifestation. Abstract Ageing and obesity are both characterized by inflammation and a deterioration in metabolic health. It is now clear that adipose tissue plays a major role in inflammation and metabolic control in obesity, although little is known about the role of adipose tissue in human ageing. To understand how ageing impacts adipose tissue, we characterized subcutaneous adipose tissue and skeletal muscle samples from twelve younger (27 ± 4 years [Young]) and twelve older (66 ± 5 years [Old]) active/non-obese males. We performed a wide-range of whole-body and tissue measures, including RNA-sequencing and multicolour flow cytometry. We also measured a range of inflammatory and metabolic proteins in the circulation and their release by adipose tissue, ex vivo. Both adipose tissue and muscle had ∼2-fold more immune cells per gram of tissue with ageing. In adipose tissue, this immune cell infiltration was driven by increased memory/effector T-cells, whereas, in muscle, the accumulation was driven by memory/effector T-cells and macrophages. Transcriptomic analysis revealed that, with ageing, adipose tissue, but not muscle, was enriched for inflammatory transcripts/pathways related to acquired and innate immunity. Ageing also increased the adipose tissue pro-inflammatory secretory profile. Insulin signalling protein content was reduced in adipose tissue, but not muscle. Our findings indicate that adipose tissue undergoes substantial immunometabolic changes with ageing in humans, and that these changes are tissue-specific and more profound than those observed in the circulation and skeletal muscle.

Context Adipose tissue and physical inactivity both influence metabolic health and systemic inflammation, but how adipose tissue responds to chronic physical inactivity is unknown. Objective This work aimed to characterize the impact of chronic physical inactivity on adipose tissue in healthy, young males. Methods We collected subcutaneous adipose tissue from 20 healthy, young men before and after 60 days of complete bed rest with energy intake reduced to maintain energy balance and fat mass. We used RNA sequencing, flow cytometry, ex vivo tissue culture, and targeted protein analyses to examine adipose tissue phenotype. Results Our results indicate that the adipose tissue transcriptome, stromal cellular compartment, and insulin signaling protein abundance are largely unaffected by bed rest when fat mass is kept stable. However, there was an increase in the circulating concentration of several adipokines, including plasma leptin, which was associated with inactivity-induced increases in plasma insulin and absent from adipose tissue cultured ex vivo under standardized culture conditions. Conclusion Physical inactivity–induced disturbances to adipokine concentrations such as leptin, without changes to fat mass, could have profound metabolic implications outside a clinical facility when energy intake is not tightly controlled.

Objective This study investigated the effect of 3 weeks of high‐sugar (“Sweet”) versus low‐sugar (“Plain”) breakfast on energy balance, metabolic health, and appetite. Methods A total of 29 healthy adults (22 women) completed this randomized crossover study. Participants had pre‐ and postintervention appetite, health, and body mass outcomes measured, and they recorded diet, appetite (visual analogue scales), and physical activity for 8 days during each intervention. Interventions were 3 weeks of isoenergetic Sweet (30% by weight added sugar; average 32 g of sugar) versus Plain (no added sugar; average 8 g of sugar) porridge‐based breakfasts. Results Pre‐ to postintervention changes in body mass were similar between Plain (Δ 0.1 kg; 95% CI: −0.3 to 0.5 kg) and Sweet (Δ 0.2 kg; 95% CI: −0.2 to 0.5 kg), as were pre‐ to postintervention changes for biomarkers of health (all P ≥ 0.101) and psychological appetite (all P ≥ 0.152). Energy, fat, and protein intake was not statistically different between conditions. Total carbohydrate intake was higher during Sweet (287 ± 82 g/d vs. 256 ± 73 g/d; P = 0.009), driven more by higher sugar intake at breakfast (116 ± 46 g/d vs. 88 ± 38 g/d; P