Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain ␣-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1␣ subunit) was significantly reduced by 35-50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferatoractivated receptor-␥ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-D-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. bariatric; diabetes; hyperinsulinemia; mammalian target of rapamycin; protein IN THE SEARCH FOR BIOMARKERS that associate with or predict type 2 diabetes mellitus (T2DM), it has become appreciated that circulating concentrations of the branched-chain amino acids (BCAA; valine, leucine, isoleucine) are often increased in obese, insulin-resistant states and in T2DM. Higher fasting plasma BCAA concentrations were initially reported in obese subjects by Adibi and by Felig et al. (2,12). Recent metabolomic studies found that plasma concentrations of BCAAs and large neutral amino acids are negatively correlated with insulin sensitivity in overweight and obese subjects (24), whereas the principal component that differentiated lean and obese individuals contained BCAA, methionine, phenylalanine, and tyrosine, with a linear relationship between plasma BCAA and homeostasis model assessment of insulin resistance (HOMA-IR) (36). Plasma concentrations of leucine and valine, as well as the leucine metabolite ␣-ketoisocaproate, were increased in obese female African-American T2DM subjects compared with age-and body mass index (BMI)-matched nondiabetic subjects, and plasma leucine significantly correlated with hemoglobin A ...

3D bioprinting strategies in tissue engineering aim to fabricate clinically applicable tissue constructs that can replace the damaged or diseased tissues and organs. One of the main prerequisites in 3D bioprinting is finding an appropriate bioink that provides a tissue‐specific microenvironment supporting the cellular growth and maturation. In this respect, decellularized extracellular matrix (dECM)‐derived hydrogels have been considered as bioinks for the cell‐based bioprinting due to their capability to inherit the intrinsic cues from native ECM. Herein, a photo‐crosslinkable kidney ECM‐derived bioink (KdECMMA) is developed that could provide a kidney‐specific microenvironment for renal tissue bioprinting. Porcine whole kidneys are decellularized through a perfusion method, dissolved in an acid solution, and chemically modified by methacrylation. A KdECMMA‐based bioink is formulated and evaluated for rheological properties and printability for the printing process. The results show that the bioprinted human kidney cells in the KdECMMA bioink are highly viable and mature with time. Moreover, the bioprinted renal constructs exhibit the structural and functional characteristics of the native renal tissue. The potential of the tissue‐specific ECM‐derived bioink is demonstrated for cell‐based bioprinting that could enhance the cellular maturation and eventually tissue formation.

Although males exhibit higher adropin levels that are reduced by obesity, aging and markers of insulin resistance are associated with low plasma adropin irrespective of sex.