Daniel A. Antwi

Brain Regulation of Appetite and Satiety

Interest in the control of feeding has increased as a result of the obesity epidemic and rising incidence of metabolic diseases. The brain detects alterations in energy stores and triggers metabolic and behavioral responses designed to maintain energy balance. Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem, whereas reward and motivation aspects of eating behavior are controlled by neurons in limbic regions and the cerebral cortex. This article provides an integrated perspective on how metabolic signals emanating from the gastrointestinal tract, adipose tissue, and other peripheral organs target the brain to regulate feeding, energy expenditure, and hormones. The pathogenesis and treatment of obesity and abnormalities of glucose and lipid metabolism are discussed.

Inhibition of ADRP prevents diet-induced insulin resistance

Diets with high fat content induce steatosis, insulin resistance, and type 2 diabetes. The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 wk. Glucose homeostasis was assessed with clamp and tracer techniques. ADRP ASO decreased the levels of triglycerides and diacylglycerol in the liver, but fatty acids, long-chain fatty acyl CoAs, ceramides, and cholesterol were unchanged. Insulin action in the liver was enhanced after ADRP ASO treatment, whereas muscle and adipose tissue were not affected. ADRP ASO increased the phosphorylation of insulin receptor substrate (IRS)1, IRS2, and Akt, and decreased gluconeogenic enzymes and PKCepsilon, consistent with its insulin-sensitizing action. These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance.

Micro- and Macroelemental Composition and Safety Evaluation of the Nutraceutical Moringa oleifera Leaves

Moringa oleifera is a multipurpose plant used in Ghana and most parts of Africa. Its high mineral, protein, and vitamins content has enabled its use as a nutraceutical and panacea for various diseases. This study aimed at measuring the micro- and macroelements content of dried Moringa oleifera leaves using energy dispersive X-ray fluorescence spectroscopic (EDXRF) and assessing its toxicological effect in rats. Acute toxicity (5000 mg/kg) and a subacute toxicity studies of the leaf (40 mg/kg to 1000 mg/kg) extract were conducted in rats. Blood samples were assessed for biochemical and haematological parameters. Results showed significant levels of thirty-five (35) elements (14 macroelements and 21 microelements) in M. oleifera extract. There were no observed overt adverse reactions in the acute and subacute studies. Although there were observed elevations in liver enzymes ALT and ALP (P < 0.001) and lower creatinine levels in the extract treated groups, no adverse histopathological findings were found. Moringa oleifera dried leaf extract may, therefore, be reasonably safe for consumption. However, the consumption of Moringa oleifera leaves should not exceed a maximum of 70 grams per day to prevent cumulative toxicity of these essential elements over long periods.

Peripheral sensory neuropathy in type 2 diabetes patients: A case control study in Accra, Ghana

Highlights • PSN was assessed by symptoms, examination and quantitative assessment.• High burden of PSN in diabetes patients in Ghana.• The major determinants of PSN using different assessment methods were reported.

Arterial Stiffness in Nonhypertensive Type 2 Diabetes Patients in Ghana

Background. Increased arterial stiffness is an independent cardiovascular risk factor in diabetes patients and general population. However, the contribution of diabetes to arterial stiffness is often masked by coexistent obesity and hypertension. In this study, we assessed arterial stiffness in nonhypertensive, nonobese type 2 diabetes (T2DM) patients in Ghana. Methods. In case-control design, 166 nonhypertensive, nonobese participants, comprising 96 T2DM patients and 70 nondiabetes controls, were recruited. Peripheral and central blood pressure (BP) indices were measured, and arterial stiffness was assessed as aortic pulse wave velocity (PWVao), augmentation index (AIx), cardioankle vascular index (CAVI), and heart-ankle pulse wave velocity (haPWV). Results. With similar peripheral and central BP indices, T2DM patients had higher PWVao (8.3 ± 1 versus 7.8 ± 1.3, p = 0.044) and CAVI (7.9 ± 1.2 versus 6.9 ± 0.7, p = 0.021) than nondiabetic control. AIx and haPWV were similar between T2DM and nondiabetic controls. Multiple regression models showed that, in the entire study participants, the major determinants of PWVao were diabetes status, age, gender, systolic BP, and previous smoking status (β = 0.22, 0.36, 0.48, 0.21, and 0.25, resp.; all p < 0.05); the determinants of CAVI were diabetes status, age, BMI, heart rate, HbA1c, total cholesterol, HDL cholesterol, and previous smoking status (β = 0.21, 0.38, 0.2, 0.18, 0.24. 0.2, −0.19, and 0.2, resp.; all p < 0.05). Conclusion. Our findings suggest that nonhypertensive, nonobese T2DM patients have increased arterial stiffness without appreciable increase in peripheral and central pressure indices.

Nitric oxide dysregulation in the pathogenesis of preeclampsia among Ghanaian women

Background Preeclampsia (PE) is still a disease of theories as the exact cause remains uncertain. Widespread vascular endothelial cell dysfunction is thought to mediate the generalized vasospasm and hypertension characteristic of PE. Altered nitric oxide (NO) production has been associated with the endothelial dysfunction in the pathogenesis of PE but conflicting results have emerged from previous studies. Objectives To determine maternal serum levels of NO, a biomarker of endothelial function, in nonpregnant, normal pregnant, and preeclamptic women. Materials and methods This was a cross-sectional case–control study of 277 women comprising 75 nonpregnant, 102 normal pregnant, and 100 preeclamptic women conducted at the Korle Bu Teaching Hospital between April and June 2011. About 5 mL of venous blood was obtained from the participants for the various investigations after meeting the inclusion criteria and signing to a written consent. Serum levels of NO were determined by Griess reaction. The data obtained were analyzed with SPSS version 20. Results The study showed significantly elevated serum levels of NO in preeclamptic women (82.45±50.31 μM) compared with normal pregnant (33.12±17.81 μM) and nonpregnant (16.92±11.41 μM) women with P<0.001. The alteration in maternal serum NO levels was significantly more profound in early-onset (severe) PE (119.63±45.860 μM) compared to that of late-onset (mild) disease (62.44±40.44 μM) with P<0.001, indicating a more severe vascular endothelial cell dysfunction in the early-onset disease. Conclusion This study has determined a profound NO upregulation in PE evidenced by significant elevation of NO metabolite levels compared to normal pregnancy. This might be due to deranged endothelial function with dysregulated production of NO to restore the persistent hypertension characteristic of PE.

Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats

ETHNOPHARMACOLOGICAL RELEVANCE Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. MATERIALS AND METHODS Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. RESULTS There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. CONCLUSION Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.

Impaired renal function and increased urinary isoprostane excretion in Ghanaian women with pre-eclampsia

Background The cause of pre-eclampsia remains largely unknown, but oxidative stress (an imbalance favoring oxidant over antioxidant forces) has been implicated in contributing to the clinical symptoms of hypertension and proteinuria. Assessment of oxidative stress in pre-eclampsia using urinary isoprostane has produced conflicting results, and it is likely that renal function may affect isoprostane excretion. The aim of this study was to determine the role of oxidative stress in the pathophysiology of pre-eclampsia and to assess the effect of renal function on isoprostane excretion in pre-eclampsia in the Ghanaian population. Methods This was a case-controlled study, comprising 103 pre-eclamptic women and 107 normal pregnant controls and conducted at the Korle-Bu Teaching Hospital between December 2006 and May 2007. The study participants were enrolled in the study after meeting the inclusion criteria and signing their written informed consent. Oxidative stress was determined by measuring urinary excretion of isoprostane and total antioxidant capacity using an enzyme-linked immunosorbent assay technique. Renal function was assessed by calculating the estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula. Results The pre-eclampsia group had significantly (P = 0.0006) higher urinary isoprostane excretion (2.81 ± 0.14 ng/mg creatinine) than the control group (2.01 ± 0.18 ng/mg creatinine) and a significantly (P = 0.0008) lower total antioxidant power (1.68 ± 0.05 mM) than the control group (1.89 ± 0.04 mM). Urinary isoprostane excretion showed a positive correlation with both mean arterial pressure (r = 0.261) and microalbuminuria (r = 0.510) in the pre-eclampsia cases. The pre-eclampsia group had a significantly lower estimated glomerular filtration rate than the control group (P < 0.001), indicating more renal impairment. Conclusion The increased urinary excretion of isoprostanes and decreased total antioxidant power in the in pre-eclampsia group suggest increased production of oxidants and depletion and/or reduction of maternal antioxidants. Increased oxidative stress may be important in the pathophysiology of pre-eclampsia by contributing to endothelial dysfunction, proteinuria, and hypertension.

Circulating Angiogenic Growth Factors in Diabetes Patients with Peripheral Arterial Disease and Exertional Leg Pain in Ghana

Objective Peripheral arterial disease (PAD) is a common complication of diabetes, associated with impairment in angiogenesis. Angiogenesis is regulated by angiogenic growth factors such as angiopoietin 1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF). We studied the association between angiogenic growth factors versus PAD and exertional leg symptoms in diabetes patients in Ghana. Method In this cross-sectional study, ankle-brachial index was measured with oscillometrically and exertional leg symptoms were screened with Edinburgh claudication questionnaire in 140 diabetes patients and 110 nondiabetes individuals. Circulating levels of Ang-1, Ang-2, and VEGF were measured with immunosorbent assay. Results The prevalence of PAD and exertional leg pain was 16.8% and 24.8%, respectively. Compared to non-PAD participants, PAD patients had higher VEGF levels [85.8 (37.5–154.5) versus 57.7 (16.6–161.1) p = 0.032] and lower Ang-1 levels [31.3 (24.8–42.6) versus 40.9 (28.2–62.1), p = 0.017]. In multivariable logistic regression, patients with exertional leg pain had increased the odds of plasma Ang-2 levels [OR (95% CI): 2.08 (1.08–6.41), p = 0.036]. Conclusion Diabetes patients with PAD and exertional leg pain have imbalance in angiogenic growth factors, indicating impaired angiogenesis. In patients with exertional leg pains, Ang-2 may be an important biomarker.

Effect of natural cocoa powder supplementation on oxidative stress in healthy Ghanaians.

Introduction: Natural cocoa powder (NCP) has been recognized to possess significant amounts of flavonoids and methylxanthines with healthful benefits. Little or no work has been done on adult Ghanaians involving supplementation with NCP. We hypothesized that chronic consumption of NCP would improve oxidative stress biomarkers and endothelial integrity. Aims: The study aimed at evaluating the long term effect of NCP supplementation on selected oxidative stress biomarkers in healthy adult Ghanaians. Study Design: This was a longitudinal intervention study design.