The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.

Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.

Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses. Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases.

Complications Following Partial and Total Wrist Arthroplasty: A Single-Center Retrospective Review.

PURPOSE: To describe our institution's experience with complications following partial and total wrist arthroplasty (TWA). METHODS: We performed a retrospective review of 105 wrist surgeries in 100 patients who underwent surgery with prosthetic replacement of the distal radius, the proximal carpus, or both at a single institution. Patient factors including age, sex, body mass index, handedness, underlying disease, and previous injury were recorded. Outcomes focused particularly on postoperative complications and need for revision surgery. RESULTS: Forty-seven TWAs, 52 distal radius hemiarthroplasties, and 6 proximal carpal hemiarthroplasties were reviewed with a mean follow-up duration of 35 ± 28 months. Overall complication and revision rates were 51% (53 of 105) and 39% (41 of 105), respectively. Postoperative contracture accounted for the largest number of complications needing additional surgery (20%), followed by component failure (15%). Deep infections occurred in 2 TWAs and 1 distal radius hemiarthroplasty and required removal of hardware, antibiotic spacer placement, and a prolonged course of intravenous antibiotics prior to a definitive operation. Of those patients requiring additional surgery, 41% (n = 10) underwent at least 2 procedures, and 10% (n = 4) underwent at least 6 additional surgeries. CONCLUSIONS: Although TWA and partial wrist arthroplasty are attractive treatment options for the painful arthritic wrist, there remains a noteworthy potential for complications requiring additional surgery. A detailed understanding of these risks is essential for surgeons so that patients may be counseled accordingly and that alternative treatment options may be considered. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Septic Sacroiliitis in a 53-Year-Old Adult: A Case Report.

A 53-year-old woman with no significant medical history presented with 10/10 right buttock pain that radiated to the right groin. With no reported recent injury, the absence of fever, and no identifiable risk factors, an infectious etiology, including septic sacroiliitis (SSI), is at the end spectrum of the differential. SSI is a rare condition with nonspecific findings that can lead to major complications, including death. To our knowledge, there are only 4 recent major literature reviews on SSI, with most cases reported to have at least 1 risk factor or clinical sign indicating the possibility of an infectious etiology. The patient reported in this case had no identifiable risk factors; therefore, high clinical suspicion is needed to prevent debilitating consequences from prolonged infection. LEVEL OF EVIDENCE: V.

A smooth muscle-like origin for beige adipocytes.

Thermogenic UCP1-positive cells, which include brown and beige adipocytes, transform chemical energy into heat and increase whole-body energy expenditure. Using a ribosomal profiling approach, we present a comprehensive molecular description of brown and beige gene expression from multiple fat depots in vivo. This UCP1-TRAP data set demonstrates striking similarities and important differences between these cell types, including a smooth muscle-like signature expressed by beige, but not classical brown, adipocytes. In vivo fate mapping using either a constitutive or an inducible Myh11-driven Cre demonstrates that at least a subset of beige cells arise from a smooth muscle-like origin. Finally, ectopic expression of PRDM16 converts bona fide vascular smooth muscle cells into Ucp1-positive adipocytes in vitro. These results establish a portrait of brown and beige adipocyte gene expression in vivo and identify a smooth muscle-like origin for beige cells.