The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies.Body weight was stable during the acute treatment period and decreased by 6.0+/-0.8 kg in those patients completing 3 months of sibutramine treatment (P<0.05). Circulating endocannabinoids and the expression of ECS genes did not change with acute or chronic sibutramine treatment.The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity.

Sibutramine

Rimonabant

10.1038/oby.2008.47

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Citations (21)

Who and What Drove Walter Kempner?

Hypertension (2014)

Philip Klemmer Clarence E. Grim Friedrich C. Luft

10.1161/hypertensionaha.114.03946

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Citations (21)

Optimal heart failure therapy and successful cardioversion in heart failure patients with atrial fibrillation

American Heart Journal (2008)

Leif‐Hendrik Boldt Sascha Rolf Martin Huemer Abdul Shokor Parwani Friedrich C. Luft

10.1016/j.ahj.2007.12.015

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Citations (25)

Support for linkage of familial combined hyperlipidemia to chromosome 1q21–q23 in Chinese and German families

Clinical Genetics (2000)

Wei-dong Pei Heike Baron Bertram Müller‐Myhsok Hans Knoblauch Said Ali Al‐Yahyaee

We examined familial combined hyperlipidemia (FCHL) families from nonisolated regions in Germany and China to see if we could corroborate support for a chromosome 1q FCHL locus in more general populations. We recruited 24 German families with 137 members, 92 of whom met the criteria of affected in terms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 families with a total of 81 members. All affected persons had total cholesterol concentrations> 240 mg/dl and triglyceride concentrations> 250 mg/dl. We examined the markers APOA2, D1S1677, D1S104, D1S194, D1S426, and D1S196. Two‐point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proportion of linked families at 36%. This marker is adjacent to D1S104. The evidence for linkage was roughly the same both in the German (HLOD 1.40) and Chinese families (HLOD 1.52). Marker D1S194 is close to the retinoid X receptor (RXR) gene locus, which was found to be linked to triglyceride levels in an earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a gene for FCHL on chromosome 1q. Furthermore, since D1S194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involvement in FCHL.

Genetic linkage

10.1034/j.1399-0004.2000.570105.x

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Citations (79)

Pharmacokinetics of Common Antibiotics Used in Continuous Ambulatory Peritoneal Dialysis

American Journal of Kidney Diseases (1983)

C. Martin Bunke George R. Aronoff Friedrich C. Luft

10.1016/s0272-6386(83)80025-0

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Citations (17)

Comparative nephrotoxicity of SCH 21420 and amikacin in rats

Antimicrobial Agents and Chemotherapy (1979)

Laura I. Rankin Friedrich C. Luft M N Yum Rebecca Sloan C B Dinwiddie

The nephrotoxic potentials of the new aminoglycoside SCH 21420 and amikacin were compared in a rat model. Groups of rats received 100, 200, 300, or 600 mg of either drug per kg per day for 14 days. Enzymuria, urine osmolality, protein excretion, and blood urea nitrogen were monitored at periodic intervals, whereas creatinine clearance and pathological changes were determined at sacrifice. Amikacin caused more enzymuria at the two lower doses as well as greater proteinuria and blood urea nitrogen elevations at the highest dose than did SCH 21420 (P less than 0.05). Pathological changes were more severe with amikacin than with SCH 21420 at the three lower doses (P less than 0.05); however, at the 600 mg/kg per day dose, the pathological scores and creatinine clearances of animals receiving either drug were not significantly different (P greater than 0.05).

Nephrotoxicity

Amikacin

Blood urea nitrogen

10.1128/aac.16.4.491

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Citations (17)

Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor

Journal of Clinical Investigation (1999)

Gerd Wallukat Volker Homuth Thorsten Fischer Carsten Lindschau B. Horstkamp

Immune mechanisms and the renin–angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor–mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti–human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II–induced vascular lesions in these patients.

10.1172/jci4106

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Citations (804)

Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats

Brain Research (2001)

Torsten Kirsch Maren Wellner Friedrich C. Luft Hermann Haller Andrea Lippoldt

Suppression subtractive hybridization

Spontaneously hypertensive rat

Stroke

10.1016/s0006-8993(01)02670-1

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Citations (68)