Plantar Flexion-Induced Entrapment of the Dorsalis Pedis Artery in a Teenaged Cross-Country Runner.

BACKGROUND: Symptomatic peripheral artery disease of the lower extremity rarely affects young adults and, when present, typically has a nonatherosclerotic etiology. Anatomical variants have manifested as symptomatic foot ischemia in four cases in the literature. We describe the case of a 17-year-old girl presenting with foot pain upon plantar flexion due to dynamic dorsalis pedis (DP) artery entrapment by fibrous bands and the extensor hallucis brevis (EHB) tendon. METHODS: The patient was a 17-year-old girl who presented with right foot pain upon plantar flexion, which resolved upon returning to the neutral position. The potential site of compression was identified on MRI where the DP artery ran deep to the EHB tendon near the first and second tarsometatarsal joints. On diagnostic arteriogram, there was notching of the dorsalis pedis over the talus bone. The dorsalis pedis Doppler signal was obliterated upon plantar flexion. A longitudinal incision was made over the artery in the area of compression. The flexor retinaculum was incised. Abnormal fibrous bands were identified, which were lysed anterior to the artery. The EHB tendon was released and transferred distally to the extensor hallucis longus tendon. RESULTS: A completion angiogram showed a persistently patent dorsalis pedis artery with plantar flexion. She was discharged one day postoperatively without issues. On follow-up, the patient was ambulatory with complete resolution of her pain. Arterial duplex demonstrated normal velocities through the dorsalis pedis in all positions. CONCLUSIONS: Symptomatic peripheral artery disease is a rare presentation in young adults and is usually due to nonatherosclerotic pathophysiology. We present a rare case of dorsalis pedis artery entrapment syndrome. Given the mechanical nature of obstruction, surgical correction was an effective treatment.

Effects of ERß and ERα on OVX-induced changes in adiposity and insulin resistance.

Loss of ovarian hormones leads to increased adiposity and insulin resistance (IR), increasing the risk for cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the molecular mechanism behind the adverse systemic and adipose tissue-specific metabolic effects of ovariectomy requires loss of signaling through estrogen receptor alpha (ERα) or estrogen receptor ß (ERß). We examined ovariectomized (OVX) and ovary-intactwild-type (WT), ERα-null (αKO), and ERß-null (ßKO) female mice (age ~49 weeks; n = 7-12/group). All mice were fed a phytoestrogen-free diet (<15 mg/kg) and either remained ovary-intact (INT) or were OVX and followed for 12 weeks. Body composition, energy expenditure, glucose tolerance, and adipose tissue gene and protein expression were analyzed. INT αKO were ~25% fatter with reduced energy expenditure compared to age-matched INT WT controls and ßKO mice (all P < 0.001). Following OVX, αKO mice did not increase adiposity or experience a further increase in IR, unlike WT and ßKO, suggesting that loss of signaling through ERα mediates OVX-induced metabolic dysfunction. In fact, OVX in αKO mice (i.e., signaling through ERß in the absence of ERα) resulted in reduced adiposity, adipocyte size, and IR (P < 0.05 for all). ßKO mice responded adversely to OVX in terms of increased adiposity and development of IR. Together, these findings challenge the paradigm that ERα mediates metabolic protection over ERß in all settings. These findings lead us to suggest that, following ovarian hormone loss, ERß may mediate protective metabolic benefits.

Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.

Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies. Thus, the role that FGF21 plays in mediating the positive metabolic effects of exercise in AT are unclear. In this study, FGF21-knockout (KO) mice were used to directly assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice were provided running wheels or remained sedentary for 8 weeks (n = 9-15/group) and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR) and AT inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased relative mass, both normalized by EX. WAT and BAT inflammation was elevated in FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene expression, citrate synthase activity, COX I content and total AMPK content in WT but not FGF21KO mice. Collectively, these findings reveal a previously unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support that FGF21 is necessary for EX-mediated anti-inflammatory effects.