Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways (AU)

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Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1ß, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.

Activation of transient receptor potential vanilloid 1 inhibits RhoA/Rho kinase and improves vasorelaxation dysfunction mediated by high-fat diet in mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms.</p><p><b>METHODS</b>A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.4, RhoA and Rho kinase in aorta were examined.</p><p><b>RESULTS</b>Compared with ND group, both nitroglycerin [(18.9 +/- 13)% vs. 100%, P < 0.01] and acetylcholine [(26 +/- 12)% vs. 100%, P < 0.01] induced vasorelaxation of aortic rings were significantly reduced in HD group. Both endothelium dependent and independent aortic rings vasorelaxation in HC group were significantly improved compared with that in HD group [acetylcholine: (69 +/- 15)%; nitroglycerin: (46.5 +/- 6)%, P < 0.05], but still reduced compared with that in ND group (P < 0.05, P < 0.01). High fat diet induced the expression of RhoA and Rho kinase. Dietary capsaicin down-regulated the expression of RhoA and Rho kinase but up-regulated the expression of Kv1.4 in aorta in mice fed with normal or high fat diet (all P < 0.05).</p><p><b>CONCLUSION</b>Dietary capsaicin can ameliorate vasorelaxation dysfunction mediated by high-fat diet. The potential mechanisms may be related with TRPV1 activation, which in turn stimulates potassium channel and inhibits RhoA and Rho kinase in the vasculature.</p>

Effect of beta-adrenoceptor on NO-induced attenuation in spontaneous contractions of ileum in mice / 中国应用生理学杂志

<p><b>AIM</b>To investigate the influence of L-arginine (NO donors, L-Arg) on spontaneous contractions of ileum in mice and study the effects of activation of beta-adrenoceptor on NO-induced inhibition in spontaneous contractions of ileum.</p><p><b>METHODS</b>The method of spontaneous contractions recording was used to investigate the effect of L-NNA, ODQ, Isoprenaline( beta-adrenoceptor agonist) and Propranolol (beta-adrenoceptor antagonist) on NO-induced inhibition in spontaneous contractions of ileum.</p><p><b>RESULTS</b>(1) L-Arg inhibited the spontaneous contractions of ileum and had concentration-response relationship. (2) L-NNA (3 x 10(-4) mol/L), ODQ (3 x 10(-6) mol/L) relieved the inhibitory effect of L-Arg in ileum . (3) Propronalol (3 x 10(-6) mol/L) decreased significantly the inhibitory effect of L-Arg. (4) Iso (1 x 10(-7) mol/L) increased the inhibitory effect of L-Arg. After Iso (1 x 10(-7) mol/L) and Propronalol (3 x 10(-6) mol/L) being coapplied, the inhibitory effect of L-Arg was not changed.</p><p><b>CONCLUSION</b>NOS catalyzed L-Arg and produced NO. NO exerted its inhibitory effect by the cGMP pathway, the activation of beta-adrenoceptor was partly involved in NO-induced relaxation in ileum.</p>

Renin-angiotensin system in mesenteric adipose tissues in rats with metabolic syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the renin-angiotensin system (RAS) in mesenteric adipose tissues and effect of angiotensin II on adipocyte differentiation.</p><p><b>METHODS</b>Thirty normal 8-week-old male Wistar rats were divided into groups on normal diet and high-fat diet. The rats on high-fat diet for 24 weeks developed the metabolic syndrome respectively. The mRNA and protein expression of mesenteric adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Lipid drop in 3T3-L1 preadipocytes and mature adipocytes were observed using oil-red O staining. The fluorescence microscope was used to detect cytosolic-free calcium in 3T3-L1 preadipocytes and mature adipocytes.</p><p><b>RESULTS</b>The expressions of angiotensinogen, angiotensin converting enzyme, angiotensin II receptor type 1 in mesenteric adipose tissue were significantly increased in rats with metabolic syndrome compared with those in rats on normal diet (P <0. 05, P <0. 01). After administration of angiotensin II , no lipid droplet in 3T3 -L1 preadipocytes and adipocytes were observed, however, intensive lipid droplet in adipocyte was found after administration of captopril and candesartan. Angiotensin II increased the intracellular-free calcium concentration in preadipocytes (P < 0. 01 ) , which was blocked by captopril and candesartan; in contrast, angiotensin II effect was blunt in mature adipocyte. Captopril and candesartan partially recovered the angiotensin II -mediated increase of cytosolic-free calcium.</p><p><b>CONCLUSION</b>RAS in the mesenteric adipose tissues is active in rats with metabolic syndrome, and antagonization of RAS can recover the lipogenesis of adipocyte.</p>