scholarly journals Lemon Extract Reduces Angiotensin Converting Enzyme (ACE) Expression and Activity and Increases Insulin Sensitivity and Lipolysis in Mouse Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2348
Author(s):  
Shilpa Tejpal ◽  
Alan M. Wemyss ◽  
Claire C. Bastie ◽  
Judith Klein-Seetharaman

Obesity is associated with insulin resistance and cardiovascular complications. In this paper, we examine the possible beneficial role of lemon juice in dieting. Lemon extract (LE) has been proposed to improve serum insulin levels and decrease angiotensin converting enzyme (ACE) activity in mouse models. ACE is also a biomarker for sustained weight loss and ACE inhibitors improve insulin sensitivity in humans. Here, we show that LE impacts adipose tissue metabolism directly. In 3T3-L1 differentiated adipocyte cells, LE improved insulin sensitivity as evidenced by a 3.74 ± 0.54-fold increase in both pAKT and GLUT4 levels. LE also induced lipolysis as demonstrated by a 16.6 ± 1.2 fold-change in pHSL protein expression levels. ACE gene expression increased 12.0 ± 0.1 fold during differentiation of 3T3-L1 cells in the absence of LE, and treatment with LE decreased ACE gene expression by 80.1 ± 0.5% and protein expression by 55 ± 0.37%. We conclude that LE’s reduction of ACE expression causes increased insulin sensitivity and breakdown of lipids in adipocytes.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Harshita Chodavarapu ◽  
Hari K Somineni ◽  
Esam Salem ◽  
Mariana Morris ◽  
Khalid M Elased

TACE, also known as ADAM17, is involved in the ectodomain shedding of several membrane bound proteins. Angiotensin converting enzyme 2 (ACE2), homologue of angiotensin converting enzyme (ACE), is known to be renoprotective by increasing the degradation of vasoactive peptide Angiotensin II (Ang II) to vasodilator peptide Ang - (1-7). It has been shown before that TACE mediates regulated ectodomain shedding of ACE2. PPARγ agonist, rosiglitazone, is known to impart renoprotection by attenuating albuminuria. However, the exact mechanism of renoprotection is not clear. Our previous results and others showed that renal ACE2 protein expression is increased during early stages of diabetes in db/db mice. We also demonstrated increased urinary ACE2 excretion in db/db mice. The goal of this study is to test the hypothesis that TACE is upregulated in db/db diabetic mice and treatment with rosiglitazone imparts renoprotection by attenuating the shedding of renal ACE2 via downregulating TACE protein expression. Male 6 week db/db mice were fed rosiglitazone (20mg/kg/day) for 10 weeks. Metabolic and urinary parameters were monitored weekly. Kidney lysate and urine was used to perform western blot and ACE2 activity (pmols/h/μg protein) respectively. db/db mice demonstrated glucose intolerance, hyperglycemia (348.2±29.9 mg/dL), and albuminuria (0.3±0.05 mg/day) at a very early age. Chronic rosiglitazone treatment normalized blood glucose levels (142.0±12.2 mg/dL), improved glucose tolerance and decreased albuminuria (0.17±0.03 mg/day) in treated db/db mice. Western blot showed increased renal TACE protein expression of db/db mice compared to controls (p<0.05). Treatment with rosiglitazone significantly decreased renal TACE protein expression in treated db/db mice compared to untreated mice (p<0.05). In addition, db/db mice demonstrated a 7 fold increase in urinary ACE2 activity (15.1±4.5) compared to controls (1.74±0.9). Treatment with rosiglitazone significantly attenuated and normalized ACE2 activity in treated db/db mice (0.1±0.06). In conclusion, TACE is upregulated in db/db mice and normalizing hyperglycemia with rosiglitazone could impart renoprotection by decreasing renal TACE protein expression and shedding of renal ACE2.


2001 ◽  
Vol 60 (3) ◽  
pp. 1124-1130 ◽  
Author(s):  
Sonoo Mizuiri ◽  
Hiromichi Hemmi ◽  
Haruko Kumanomidou ◽  
Masateru Iwamoto ◽  
Moriatsu Miyagi ◽  
...  

Author(s):  
A.Z. Dautova ◽  
E.A. Khazhieva ◽  
V.G. Shamratova ◽  
L.Z. Sadykova

The aim of the paper was to study the association of polymorphic variants of rs4646994 (I/D) of the angiotensin converting enzyme gene (ACE) and rs5810761 (+9/-9) of the bradykinin B2 receptor gene (BDKRB2) with erythrocyte adrenoreactivity (ARE) in athletes and untrained young men. Materials and Methods. The study involved 61 young men (aged 21–23) with different levels of motor activity (MA). ARE was evaluated according to the erythrocyte sedimentation rate (ESR) change under adrenaline in vitro at final concentrations 10-5, 10-6, 10-7, 10-9, 10-11, 10-13 g/ml of venous blood. According to the effect observed and ESR shifts under adrenaline, we distinguished 3 ARE types: antiaggregative (AnAg), areactive (Ar) and aggregative (Ar). Results. The results of comparative and correlation analyses demonstrated that young athletes with +9/-9 (BDKRB2) genotype were characterized by a higher aggregative resistance of erythrocytes to the effects of both physiological (<10-9 g/ml) (physiological adrenaline concentration, PAC) and stressful doses (>10-9 g/ml) of adrenaline (stress adrenaline concentration, SAC), as well as by predominance of AnAg and Ar ARE types. In athletes, among the representatives of different genotypes of АСЕ gene I/D polymorphism, the erythrocyte response to adrenaline did not have any statistically significant differences. In physically inactive students, namely individuals with the D/D genotype, maximal ESR deviation under PAC was less than in those with I/D genotype. Conclusion. Athletes with *-9 allele (+9/-9 genotype) in their genotype can be considered more stress-resistant, which is provided by optimal adaptive and compensatory body mechanisms. Apparently, resistance of cells to the adrenaline contributes much to the work of these mechanisms. As for the ACE gene polymorphism, its effect on the suspension characteristics of erythrocytes is less pronounced not only in physically inactive young men, but in athletes as well. Keywords: erythrocyte adrenoreactivity (ARE), stress tolerance, β2 bradykinin receptor gene (BDKRB2), angiotensin converting enzyme (ACE) gene, motor activity. Цель работы – изучить ассоциацию полиморфных вариантов rs4646994 (I/D) гена ангиотензинпревращающего фермента (АСЕ) и rs5810761 (+9/-9) гена рецептора брадикинина 2 типа (BDKRB2) с адренореактивностью эритроцитов (АРЭ) у спортсменов и юношей, ведущих физически малоактивный образ жизни. Материалы и методы. В исследовании принял участие 61 юноша с разным уровнем двигательной активности (ДА) в возрасте 21–23 лет. Оценку АРЭ проводили по изменению скорости оседания эритроцитов (СОЭ) под действием адреналина in vitro в конечных концентрациях 10-5, 10-6, 10-7, 10-8, 10-9, 10-11, 10-13 г/мл венозной крови. По характеру наблюдаемого эффекта в соответствии с направленностью сдвигов СОЭ в присутствии адреналина мы выделили 3 типа АРЭ: антиагрегационный (АнАг), ареактивный (Ар) и агрегационный (Аг). Результаты. По результатам сравнительного и корреляционного анализа установлено, что юноши-спортсмены с генотипом +9/-9 (BDKRB2) характеризуются более высокой агрегативной устойчивостью эритроцитов к воздействию как физиологических (10-9 г/мл и ниже), так и повышенных (стрессовых) доз (выше 10-8 г/мл крови) адреналина, а также преобладанием АнАг- и Ар-типов АРЭ. У представителей разных генотипов полиморфизма I/D гена АСЕ реакция эритроцитов на адреналин не имела статистически значимых различий в группе спортсменов, тогда как в группе малоактивных студентов у лиц с генотипом D/D максимальное отклонение СОЭ при ФКА было меньше, чем при генотипе I/D. Выводы. Спортсменов, имеющих в своём генотипе аллель *-9 (+9/-9 генотип), можно считать более стрессоустойчивыми, что обеспечивается оптимальными адаптивно-компенсаторными механизмами организма, существенная роль в обеспечении которых, по-видимому, принадлежит устойчивости клеток к действию адреналина. Что касается полиморфизма гена АСЕ, то его влияние на суспензионные характеристики эритроцитов выражено слабее не только у физически малоактивных юношей, но и у спортсменов. Ключевые слова: адренореактивность эритроцитов (АРЭ), стрессоустойчивость, ген рецептора брадикинина β2 (BDKRB2), ген ангиотензинпревращающего фермента (АСЕ), двигательная активность.


Sign in / Sign up

Export Citation Format

Share Document