leptin and temocapril-hydrochloride

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Composition; Body Weight; Diet; Fructose; Glomerulosclerosis, Focal Segmental; Hypertension; Kidney Glomerulus; Leptin; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Organ Size; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Thiazepines

The aim of this study was to evaluate the effects of moderate-intensity regular exercise and/or an angiotensin converting enzyme (ACE) inhibition on tumor necrosis factor-alpha (TNF-alpha) and glucose and lipid metabolism parameters. Spontaneously hypertensive rats (SHRs) were fed a fructose-rich diet during 16 weeks of either exercise training (Ex group: 20 m/min, 0% grade, 60 min/day, 5 days/week), administration of an ACE inhibitor (TM group: temocapril, 10 mg/kg/day), or a combination of both (TM+Ex group). The systolic blood pressure was reduced exclusively in the TM and TM+Ex group. Epididymal fat pads (EPI) weighed less in the TM+Ex group than in the single-treatment (TM) group. The serum leptin level was significantly and directly correlated with the EPI weight (p < 0.001). The TNF-alpha content per gram of EPI was the highest in the TM+Ex group. In addition, the EPI TNF-alpha level was negatively correlated with both the EPI weight and the serum leptin level (p < 0.001, respectively). In contrast, the TNF-alpha level of skeletal muscles was identical among the groups. The extensor digitorum longus had a significantly higher abundance of TNF-alpha protein than the soleus muscle. These data indicate that the local TNF-alpha expression is tissue-specific, and that upregulation of TNF-alpha in EPI by exercise training and/or ACE inhibition may have contributed to the reduction in fat cell volume via the induction of apoptosis and/or the regulation of metabolic homeostasis.

Topics: Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Diet; Epididymis; Fructose; Hindlimb; Hypertension; Leptin; Male; Motor Activity; Muscle, Skeletal; Myocardium; Organ Size; Rats; Rats, Inbred SHR; Systole; Thiazepines; Tumor Necrosis Factor-alpha; Up-Regulation