Supplementation with a New Standardized Extract of Green and Black Tea Exerts Antiadipogenic Effects and Prevents Insulin Resistance in Mice with Metabolic Syndrome.

Insulin resistance is one of the main characteristics of metabolic syndrome (MetS) and the main cause of the development of type II diabetes. The high prevalence of this syndrome in recent decades has made it necessary to search for preventive and therapeutic agents, ideally of natural origin, with fewer side effects than conventional pharmacological treatments. Tea is widely known for its medicinal properties, including beneficial effects on weight management and insulin resistance. The aim of this study was to analyze whether a standardized extract of green and black tea (ADM® Complex Tea Extract (CTE)) prevents the development of insulin resistance in mice with MetS. For this purpose, C57BL6/J mice were fed for 20 weeks with a standard diet (Chow), a diet with 56% kcal from fat and sugar (HFHS) or an HFHS diet supplemented with 1.6% CTE. CTE supplementation reduced body weight gain, adiposity and circulating leptin levels. Likewise, CTE also exerted lipolytic and antiadipogenic effects in 3T3-L1 adipocyte cultures and in the C. elegans model. Regarding insulin resistance, CTE supplementation significantly increased plasma adiponectin concentrations and reduced the circulating levels of insulin and the HOMA-IR. Incubation of liver, gastrocnemius muscle and retroperitoneal adipose tissue explants with insulin increased the pAkt/Akt ratio in mice fed with Chow and HFHS + CTE but not in those fed only with HFHS. The greater activation of the PI3K/Akt pathway in response to insulin in mice supplemented with CTE was associated with a decrease in the expression of the proinflammatory markers Mcp-1, IL-6, IL-1ß or Tnf-α and with an overexpression of the antioxidant enzymes Sod-1, Gpx-3, Ho-1 and Gsr in these tissues. Moreover, in skeletal muscle, mice treated with CTE showed increased mRNA levels of the aryl hydrocarbon receptor (Ahr), Arnt and Nrf2, suggesting that the CTE's insulin-sensitizing effects could be the result of the activation of this pathway. In conclusion, supplementation with the standardized extract of green and black tea CTE reduces body weight gain, exerts lipolytic and antiadipogenic effects and reduces insulin resistance in mice with MetS through its anti-inflammatory and antioxidant effects.

Endothelium-dependent relaxation of isolated splanchnic arteries from cirrhotic patients: Role of reactive oxygen species.

AIM: To examine the endothelium-dependent relaxation of splanchnic arteries during cirrhosis as well as the role of reactive oxygen species in this relaxation using hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors. METHODS: Arterial segments 3 mm long were mounted in organ baths for isometric tension recording and precontracted with the thromboxane A(2) analog U46619 (10(-7)-10(-6) M). RESULTS: The relaxation to acetylcholine (10(-8)-10(-4) M), but not to sodium nitroprusside (10(-8)-10(-4) M) was lower in hepatic arteries. The inhibitor of nitric oxide synthesis, N(omega)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), the inhibitor of cyclooxygenase, meclofenamate (10(-5) M), or l-NAME (10(-4) M) + meclofenamate (10(-5) M) diminished the relaxation to acetylcholine only in mesenteric arteries. l-NAME (10(-4) M) + meclofenamate (10(-5) M) combined with charybdotoxin (10(-7) M) + apamine (10(-6) M) inhibited the relaxation toacetylcholine in both types of arteries, and this inhibition was greater than with l-NAME + meclofenamate. The scavenger of hydrogen peroxide, catalase (1000 U/mL), the superoxide dismutase mimetic, tiron (10(-2) M) or the inhibitor of NAD(P)H oxidase, diphenyleneiodonium (5 x 10(-6) M), but not the inhibitor of superoxide dismutase, diethyldithiocarbamate (10(-3) M) potentiated the acetylcholine-induced relaxation only in hepatic arteries. l-NAME did inhibit the relaxation to acetylcholine in hepatic arteries pretreated with catalase or tiron. CONCLUSIONS: Cirrhosis may decrease endothelial release and/or bioavailability of nitric oxide and prostacyclin in splanchnic arteries, which might be caused partly by increased production of reactive oxygen species.

In vivo coronary effects of endothelin-1 after ischemia-reperfusion. Role of nitric oxide and prostanoids.

To examine the effects of reperfusion after short and prolonged ischemia on the coronary action of endothelin-1, left circumflex coronary artery flow was electromagnetically measured, and 15- or 60-min occlusion of this artery followed by reperfusion was induced in anesthetized goats. In non-treated animals, during reperfusion after 15-min occlusion, the duration but not the peak of endothelin-1-induced coronary effects (0.01-0.3 nmol) was increased, and the effects of acetylcholine (3-100 ng) were unchanged. During reperfusion after 60-min occlusion, the peak and duration of endothelin-1-induced effects were increased whereas those of acetylcholine were decreased. N(w)-nitro-L-arginine methyl esther (L-NAME) treatment did not modify the peak and duration of the coronary effects of endothelin-1 during reperfusion after both durations of occlusion. This treatment inhibited the effects of the two higher doses but not those of the two lower doses of acetylcholine during reperfusion after 15-min occlusion, and it did not modify the effects of any dose of this drug during reperfusion after 60-min occlusion. Meclofenamate treatment did not modify the coronary effects of endothelin-1 and acetylcholine during reperfusion after both durations of occlusion. These results suggest that ischemia-reperfusion increases the coronary response to endothelin-1, which is more pronounced during reperfusion after prolonged than after brief ischemia, and that this increased response is probably related to inhibition of nitric oxide release, without involvement of prostanoids.

Coronary reactivity to endothelin-1 during partial ischemia and reperfusion in anesthetized goats. Role of nitric oxide and prostanoids.

To examine the coronary reactivity to endothelin-1 and its interaction with nitric oxide or prostanoids during partial coronary ischemia and reperfusion, left circumflex coronary artery flow was electromagnetically measured, and partial occlusion of this artery was induced for 60 min, followed by reperfusion in anesthetized goats (eight non-treated, six treated with N(w)-nitro-L-arginine methyl esther (L-NAME) and five treated with meclofenamate). During partial occlusion, coronary vascular conductance was reduced by 24-37% (P<0.01), and the coronary vasodilatation in response to acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) was much decreased in every case; the vasoconstriction in response to endothelin-1 (1-10 microg) was depressed in non-treated animals, and this depression was reversed by L-NAME and was accentuated by meclofenamate. At 30 min of reperfusion coronary vascular conductance remained decreased by 22-27% (P<0.01), and the vasodilatation in response to acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg), as well as the vasoconstriction with endothelin-1 (1-10 microg), were as in the control and comparable in the three groups of animals. These results suggest: (a) that during ischemia, the coronary vasodilator reserve is greatly reduced, and the vasoconstriction with endothelin-1 is blunted, with preservation of the modulatory role of nitric oxide and involvement of vasoconstrictor prostanoids in this vasoconstriction, and (2) that during reperfusion, the coronary vasodilator reserve and the coronary reactivity to acetylcholine and endothelin-1 recover, but the modulatory role of nitric oxide in this reactivity may be attenuated.