Corticosteroid-triggered acute skeletal muscle loss in lipodystrophy: A case report.

The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28-year-old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.

Association of Low-Normal Free T4 Levels With Future Major Depression Development.

Context: Hyperthyroidism and overt and subclinical hypothyroidism are associated with major depression; however, the association of major depression across the spectrum of thyroid function within the normal range is unknown. Objective: We investigated whether higher or lower levels of free thyroxine (T4) and thyrotropin (TSH) within the normal range are associated with major depression. Methods: This was a retrospective cohort study of 66 960 participants with normal thyroid function who visited for health checkups (St. Luke's International Hospital, 2005-2018). The primary outcome was the development of major depression during the follow-up period. Participants were divided into 3 equal groups based on baseline free T4 or TSH values (low-, middle-, or high-normal), and the incidence of major depression was compared using the Cox proportional hazard model after adjusting for potential covariates. Results: During the median follow-up of 1883 days, 1363 (2.0%) patients developed major depression. The low-normal free T4 group had a significantly higher risk of major depression (adjusted HR 1.15; 95% CI, 1.01-1.31), but not the high-normal free T4 group or TSH groups. The association between low-normal free T4 and the development of major depression was maintained, rather more obvious, upon exclusion of participants whose thyroid hormone levels became abnormal during follow-up compared with data from all participants (adjusted HR 1.24; 95% CI, 1.07-1.43). Conclusion: In this cohort, low-normal free T4 was associated with an increased risk of future major depression, even if subsequent hormone levels were maintained within the normal range. The magnitude of the impact of low-normal free T4 was relatively mild.

AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice.

Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1.