PID1 in adipocytes modulates whole-body glucose homeostasis.

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes.

Transcriptome analysis reveals the potential contribution of long noncoding RNAs to brown adipocyte differentiation.

Brown adipose tissue (BAT) functions to dissipate energy in response to cold exposure or overfeeding. Counteracting obesity has been extensively considered as a promising target. Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the potential biological functions of lncRNAs during mouse brown fat cell differentiation have not been fully understood. Here, we performed lncRNA and mRNA expression profile analysis using microarray technology and identified 1064 lncRNAs with differential expression (fold change| ≥4, p ≤ 0.01) on day 0 and day 8 during differentiation. Furthermore, candidate lncRNAs were characterized by comprehensive examination of their genomic context, gene ontology (GO) enrichment of their associated protein-coding genes and pathway analysis. We identified three lncRNAs (Gm15051, Tmem189 and Cebpd) associated with their flanking coding genes (Hoxa1, C/EBPß and C/EBPδ), which participated in adipose commitment. Collectively, our findings indicated lncRNAs are involved in mouse BAT development and provide potential targets for obesity therapy.

The biological effects of hsa-miR-1908 in human adipocytes.

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. MiR-1908 is a recently identified miRNA that is highly expressed in human adipocytes. However, it is not known what role of miR-1908 is involved in the regulation of human adipocytes. In this study, we demonstrate that the level of miR-1908 increases during the adipogenesis of human multipotent adipose-derived stem (hMADS) cells and human preadipocytes-visceral. Overexpression of miR-1908 in hMADS cells inhibited adipogenic differentiation and increased cell proliferation, suggesting that miR-1908 is involved in the regulation of adipocyte cell differentiation and metabolism, and, thus, may have an effect on human obesity.

MiR-146b is a regulator of human visceral preadipocyte proliferation and differentiation and its expression is altered in human obesity.

Visceral obesity is an independent risk factor for metabolic syndrome, and abnormal fat accumulation is linked to increases in the number and size of adipocytes. MiR-146b was a miRNA highly expressed in mature adipocytes while very lowly expressed in human mesenchymal stem cells (hMSCs) and human visceral preadipocytes (vHPA). In this paper, we mainly focused on the roles of miR-146b in adipogenesis. We found miR-146b could inhibit the proliferation of visceral preadipocytes and promote their differentiation. MiR-146b in human visceral adipocytes inhibited the expression of KLF7, a member of the Kruppel-like transcription factors, as demonstrated by a firefly luciferase reporter assay, indicating that KLF7 is a direct target of the endogenous miR-146b. MiR-146b expression was significantly altered in visceral and subcutaneous adipose tissues in human overweight and obese subjects, and in the epididymal fat tissues and brown fat tissues of diet-induced obese mice. Our data indicates that miR-146b may be a new therapeutic target against human visceral obesity and metabolic dysfunction.

[Changes of apelin and its receptor in lung tissue of rats with pulmonary hypertension induced by monocrotaline].

OBJECTIVE: To observe the change of apelin and its receptor (APJ) in the lung tissue of rats with pulmonary hypertension induced by monocrotaline and to explore its significance. METHODS: Twenty-five male SD rats were randomly divided into control group (n = 10) and monocrotaline group (n = 15). On the twenty-first day after the rats were intraperitoneally injected 60 mg/kg monocrotaline for monocrotaline group or equal volume vehicle for control group, the mean pulmonary artery pressure was measured by right heart catheterization. Histopathological study of lung tissue was done with hematoxylin-eosin (HE) and Masson's trichrome staining. The concentration of apelin in the plasma was measured by radioimmunoassay. The expressions of apelin/APJ proteins and genes in lung tissue were measured respectively by Western blot and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary vascular remodeling index, content of apelin protein in lung tissue of monocrotaline group were higher than those in control group. APJ protein and gene expression in monocrotaline group were significantly lower than those in control group (P < 0.01, P < 0.05), but apelin gene expression in the lung tissue between the two groups had no significant difference. CONCLUSION: Endogenous apelin/APJ dysfunction may play an important role in the development of pulmonary hypertension induced by monocrotaline.

[Effect of electroacupuncture of local plus distal acupoints in the same segments of spinal cord on spinal substance P expression in rats with chronic radicular pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of local plus distal acupoints on spinal substance P expression in chronic radicular pain (CRP) rats so as to investigate its underlying mechanism in the treatment of chronic radical pain. METHODS: Twenty-five Wistar rats were randomized into control, model, local acupoints [LA, bilateral "Jiaji" (EX-B 2)], distal acupoints [DA, bilateral "Yanglingquan" (GB 34)], and LA+ DA groups, with 5 cases in each. CRP model was duplicated by implanting a gel-silicon wrapping the nerve root of L4 under anesthesia. EA (2 Hz, < or =2 mA) was applied to EX-B2 and GB34 for 30 min for 8 days. Pathological changes of the local focus tissue were observed by HE dyeing, and the animals' motor state was also observed. The pain threshold was detected by using tail-flick method. Substance P immunoreactive (IR) positive product of the spinal dorsal horn (L3-L5) was detected by immunohistochemical method and expressed as integrated optical density (IOD). RESULTS: The motor scores on day 35 after modeling and pain threshold values on day 4 and 8 after treatment in EX-B2 group, GB34 group and EX-B2 + GB34 group were significantly higher than those in model group (P < 0.05, 0.01). Compared with model group, IOD values of SP in the spinal dorsal horn in EX-B2 , GB34 and EX-B2 + GB34 groups were significantly lower (P < 0.05). There were no significant differences among the 3 EA groups in the expression of SP in the spinal dorsal horn. CONCLUSION: EA of EX-B2, GB34 and EX-B2 + GB34 all has a good analgesic effect in CRP rats, which may be realized partially by suppressing the release of SP in the spinal cord. No significant differences were found among local acupoint, distal acupoint and local plus distal acupoint groups in relieving CRP, improving motor and decreasing SP expression.