Effect of Individual Fractions Released from Myofibrils by CAF (Ca2+-activated Factor) on Z-Disk Reconstitution

To investigate the exact protein constituents of 2-disk on the basis of the success or failure of reconstitution of Z-disk, proteins released from myofibrils by CAF(Ca²⁺-activated factor) were fractionated, the Z-disk was reconstituted by incubating individual fractions with Z-disk- extracted fiber bundles and the proteins in each fraction were analyzed by polyacrylamide gel electrophoresis.Released materials from myofibrils by CAF were divided into three fractions, A, B and C, in the order of elution from a Sepharose 6B column. The materials in Fractions A and B have been bound in the Z-disk region, and the Z-disk extracted from myofibrils in a low ionic strength solution has been reconstituted. The Z-disk reconstituted by incubating the materials in Fraction A with Z-disk-extracted myofibrils seems to have a structure similar to the intact Z-disk. Fraction A consisted principally of proteins having subunit molecular weights near 100,000 and 34,000 daltons.     

Studies on Insecticidal Constituents of Juniperus recurva Buch

The active insecticidal principles in the heartwood of Juniperus recurva were found to be thujopsene and 8-cedren-13-ol. Additional 12 sesquiterpenes were also detected in the neutral fraction of ether extracts.     

p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

Proper regulation of white and brown adipogenic differentiation is important for maintaining an organism''s metabolic profile in a homeostatic state. The recent observations showing that the p53 tumor suppressor plays a role in metabolism raise the question of whether it is involved in the regulation of white and brown adipocyte differentiation. By using several in vitro models, representing various stages of white adipocyte differentiation, we found that p53 exerts a suppressive effect on white adipocyte differentiation in both mouse and human cells. Moreover, our in vivo analysis indicated that p53 is implicated in protection against diet-induced obesity. In striking contrast, our data shows that p53 exerts a positive regulatory effect on brown adipocyte differentiation. Abrogation of p53 function in skeletal muscle committed cells reduced their capacity to differentiate into brown adipocytes and histological analysis of brown adipose tissue revealed an impaired morphology in both embryonic and adult p53-null mice. Thus, depending on the specific adipogenic differentiation program, p53 may exert a positive or a negative effect. This cell type dependent regulation reflects an additional modality of p53 in maintaining a homeostatic state, not only in the cell, but also in the organism at large.     

Lactoferrin gene knockdown leads to similar effects to iron chelation in human adipocytes

In human and mice adipose tissue, lactoferrin (LTF) has been found to be associated with increased adipogenesis and decreased inflammatory markers. Here, we aimed to investigate the effects of LTF knockdown (KD) in human adipocyte differentiation. In addition, the effects of exogenous LTF administration and iron chelation [using deferoxamine (DFO, 10 μM)] were tested. In both subcutaneous and visceral pre‐adipocytes, LTF KD led to decrease significantly adipogenic, lipogenic and insulin signalling‐related gene expression and a significant increase in the gene expression of inflammatory mediators. Human lactoferrin (hLf, 1 μM) administration led to recover adipocyte differentiation in LTF KD pre‐adipocytes. Interestingly, iron chelation triggered similar effects to LTF KD, decreasing significantly adipogenic gene expressions. Of note, DFO (10 μM) and hLf (1 and 10 μM) co‐administration led to a dose‐dependent recovery of adipocyte differentiation. These new data reveal that endogenous LTF biosynthesis during human adipocyte differentiation is essential to achieve this process, possibly, modulating adipocyte iron homoeostasis. hLf administration might be a useful therapeutic target in obesity‐associated adipose tissue dysfunction.     

Curcumin prevents obesity by targeting TRAF4‐induced ubiquitylation in m6A‐dependent manner

Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown. Here, we show that the administration of curcumin significantly prevents HFD‐induced obesity and decreases the fat mass of the subcutaneous inguinal WAT (iWAT) and visceral epididymal WAT (eWAT) in mice. Mechanistically, curcumin inhibits adipogenesis by reducing the expression of AlkB homolog 5 (ALKHB5), an m⁶A demethylase, which leads to higher m⁶A‐modified TNF receptor‐associated factor 4 (TRAF4) mRNA. TRAF4 mRNA with higher m⁶A level is recognized and bound by YTHDF1, leading to enhanced translation of TRAF4. TRAF4, acting as an E3 RING ubiquitin ligase, promotes degradation of adipocyte differentiation regulator PPARγ by a ubiquitin–proteasome pathway thereby inhibiting adipogenesis. Thus, m⁶A‐dependent TRAF4 expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin‐induced obesity prevention. Our findings provide mechanistic insights into how m⁶A is involved in the anti‐obesity effect of curcumin.     

A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression

The mouse lipin gene, Lpin1, is important for adipose tissue development and is a candidate gene for insulin resistance. Here, we investigate the adipose tissue expression levels of the human LPIN1 gene in relation to various clinical variables as well as adipocyte function. LPIN1 gene expression was induced at an early step in human preadipocyte differentiation in parallel with peroxisome proliferator-activated receptor gamma. Lipin mRNA levels were higher in fat cells than in adipose tissue segments but showed no difference between subcutaneous and omental depots. Moreover, LPIN1 expression levels were reduced in obesity, improved following weight reduction in obese subjects, and were downregulated in women with the metabolic syndrome. With respect to adipocyte function, adipose LPIN1 gene expression was strongly associated with both basal and insulin-mediated subcutaneous adipocyte glucose transport as well as mRNA levels of glucose transporter 4 (GLUT4). We show that body fat accumulation is a major regulator of human adipose LPIN1 expression and suggest a role of LPIN1 in human preadipocyte as well as mature adipocyte function.