Overweight, Obesity, and Blood Pressure: The Effects of Modest Weight Reduction

MERTENS, I; Gaal, Luc F. Van

doi:10.1038/oby.2000.32

Cited by 280 publications

(185 citation statements)

References 59 publications

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“…Cetilistat (ATL-962), a novel lipase inhibitor P Kopelman et al Treatment with cetilistat also had a beneficial effect on the factors commonly associated with the risk of obesity-related co-morbidities. Modest reductions in bodyweight (5-10%) have been shown to improve glycaemic control, 18 hypertension 6 and cardiovascular disease risk. 19 Approximately 30% of patients in each treatment group achieved a weight loss of at least 5% after 12 weeks, compared to 17% in the placebo group.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] A sustained weight loss of between 5 and 10% of initial body weight has been associated with clinically meaningful reductions in these obesity-related comorbidities. [5][6][7] Effective pharmacotherapies that can produce sustained weight loss of this magnitude, when accompanied by an acceptable adverse effect profile are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

et al. 2006

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Objective: To determine the efficacy, safety and tolerability of cetilistat (ATL-962), a novel inhibitor of gastrointestinal (GI) lipases, in obese patients. Design: Phase II, multicentre, randomized, placebo-controlled, parallel group study. Enrolled patients (N ¼ 442) were advised a hypocaloric diet (deficient by 500 kcal per day, 30% of calories from fat) for a 2-week run-in period. Patients who satisfied the entry criteria (N ¼ 371) continued on the hypocaloric diet and were randomized to either placebo or one of three different doses of cetilistat (60 mg three times daily t.i.d., 120 mg t.i.d. and 240 mg t.i.d.) for 12 weeks, followed by a 4-week post-treatment follow-up. Safety, tolerability and body weight were assessed, together with other parameters associated with obesity. Outcome measures: The primary outcome measure was absolute change in body weight from baseline. Secondary outcomes included the proportion of patients achieving pre-defined weight loss targets, changes from baseline in waist circumference and in blood lipids. GI tolerability criteria were specifically assessed, as was safety. Results: Treatment with cetilistat reduced mean body weight to similar extents at all doses, which were statistically significant compared with placebo (60 mg t.i.d. 3.3 kg, Po0.03; 120 mg t.i.d. 3.5 kg, P ¼ 0.02; 240 mg t.i.d. 4.1 kg, Po0.001). Total serum and low-density lipoprotein cholesterol levels were likewise significantly reduced by 3-11% at all doses of cetilistat. Cetilistat was well tolerated. The frequency of withdrawal owing to treatment-emergent adverse events was similar between cetilistat-treated groups (5.3-7.6%) and placebo (7.6%). Adverse events were generally mild to moderate in intensity, occurred on only one occasion and were mostly GI in nature. The incidence of GI adverse events was increased in the cetilistat-treated groups compared to placebo. However, those GI adverse events, such as flatus with discharge and oily spotting, only occurred in 1.8-2.8% of subjects in the cetilistat-treated groups. Conclusions: Cetilistat produced a clinically and statistically significant weight loss in obese patients in this short-term 12-week study. This was accompanied by significant improvements in other obesity-related parameters. Cetilistat treatment was well tolerated. The risk-benefit demonstrated in this study in terms of weight loss vs intolerable GI adverse effects shows that cetilistat merits further evaluation for the pharmacotherapy of obesity and related disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

et al. 2006

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“…44 A recent study 45 found an evident association between obesity and a decrease in the expression of D 2 receptors in the brain of obese individuals (BMI Ͼ40 k/m 2 ). Since DA regulates the brain reward circuits producing an agreeable feeling as a response to certain stimuli, 46,47 deficiency in DA action in these patients could perpetuate pathological intake as a means to compensate a decrease in these circuits, the socalled Reward Deficiency Syndrome.…”

Section: Obesity and Hypertensionmentioning

confidence: 99%

Dopamine, hypertension and obesity

et al. 2002

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“…More important, this study ruled out key variables and potential confounders that could affect blood pressure. Weight loss, loss of adiposity, and increases in activity are known to have positive effects on blood pressure profiles 35, 36, 37, 38, 39. However, the experimental paradigm used in the current study uses obese mice that share similar metabolic profiles in that body mass, total fat content, oxygen consumption, and activity levels remain unchanged with or without increased muscle mass.…”

Section: Discussionmentioning

confidence: 99%

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

Butcher

Mintz

Larion

et al. 2018

JAHA

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BackgroundObesity compromises cardiometabolic function and is associated with hypertension and chronic kidney disease. Exercise ameliorates these conditions, even without weight loss. Although the mechanisms of exercise's benefits remain unclear, augmented lean body mass is a suspected mechanism. Myostatin is a potent negative regulator of skeletal muscle mass that is upregulated in obesity and downregulated with exercise. The current study tested the hypothesis that deletion of myostatin would increase muscle mass and reduce blood pressure and kidney injury in obesity.Methods and ResultsMyostatin knockout mice were crossed to db/db mice, and metabolic and cardiovascular functions were examined. Deletion of myostatin increased skeletal muscle mass by ≈50% to 60% without concomitant weight loss or reduction in fat mass. Increased blood pressure in obesity was prevented by the deletion of myostatin, but did not confer additional benefit against salt loading. Kidney injury was evident because of increased albuminuria, which was abolished in obese mice lacking myostatin. Glycosuria, total urine volume, and whole kidney NOX‐4 levels were increased in obesity and prevented by myostatin deletion, arguing that increased muscle mass provides a multipronged defense against renal dysfunction in obese mice.ConclusionsThese experimental observations suggest that loss of muscle mass is a novel risk factor in obesity‐derived cardiovascular dysfunction. Interventions that increase muscle mass, either through exercise or pharmacologically, may help limit cardiovascular disease in obese individuals.

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Overweight, Obesity, and Blood Pressure: The Effects of Modest Weight Reduction

Cited by 280 publications

References 59 publications

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

Dopamine, hypertension and obesity

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

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