Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

Valet, Philippe; Berlan, Michel; Beauville, M; Crampes, F.; Montastruc, J L; Lafontan, Max

doi:10.1172/jci114425

Cited by 78 publications

(36 citation statements)

References 19 publications

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“…100 Glucagon and corticotropin (ACTH), which are known to stimulate lipolysis in rodent fat cells, are not active in human fat cells. Other putative agents, released by exercise, such as prostaglandins, adenosine, and neuropeptide Y, 101 are known to exert antilipolytic effects on human fat cells.…”

Section: Lafontan Et Al Metabolic Role For Atrial Natriuretic Peptidementioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

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Abstract-In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. (ATP III). The NCEP definition of the metabolic syndrome includes 3 or more of the following: abdominal obesity, defined as waist circumference Ն102 cm in men and Ͼ88 cm in women; elevated triglyceride concentration Ն150 mg/dL, low HDL cholesterol (Ͻ40 mg/dL in men and Ͻ50 mg/dL in women); elevated fasting plasma glucose level (Ն110 mg/dL); and elevated blood pressure (Ն130/85 mm Hg). 1 The presence of abdominal obesity is more closely associated with the metabolic risk factors than body mass index. The prevalence of the metabolic syndrome increases with age. Obesity interferes with many metabolic pathways which underlie numerous potential risk factors. It is very difficult to differentiate between the major and minor factors, and some remain to be discovered. 2 This complexity leaves the area open and challenges basic and clinical researchers to uncover novel metabolic pathways. The discovery that cardiac natriuretic peptides (NPs) control human fat cell function is a provocative observation which reveals an unsuspected link between heart and adipose tissue. NPs exert potent lipolytic effects (eg, stimulation of hydrolysis of triacylglycerols stored in adipocytes) in isolated human fat cells. 3 When administered intravenously, they potently increase plasma glycerol and nonesterified fatty acid (NEFA) levels; in other words they stimulate lipid mobilization. 4 Before the discovery of the NP pathway, catecholamines and insulin were considered to be the major acute regulators of lipid mobilization in humans: they both act through a cAMP-dependent regulation of lipolysis. In contrast, NPs activate a 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP)-dependent pathway that is completely independent from the cAMP-dependent pathway. 5 The NPs may represent a promising new pathway contributing to the control of lipid mobilization in humans in physiological and pathological conditions. The introductory section

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Section: Lafontan Et Al Metabolic Role For Atrial Natriuretic Peptidementioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

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“…81,82 In the periphery, one of the targets on which Y1 receptors may exert effects on lipid metabolism are adipocytes, which express Y1 receptors 29,30 and which are innervated with sympathetic neurons containing NPY. 31,83 Blocking Y1-receptor signalling on isolated adipocytes from rodents and human beings in vitro antagonizes the anti-lipolytic effects of NPY and enhances lipolysis, [84][85][86][87]30 and this mechanism may contribute to the enhanced lipid oxidation seen in peripheral Y1-receptor deficiency. In addition, our findings suggest that Y1 receptors in the liver may have an important function in the regulation of lipid oxidation.…”

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confidence: 99%

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

et al. 2009

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Objective: Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1 À/À mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice. Results: Germline Y1À/À mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1 À/À mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in b-oxidation; b-hydroxyacyl CoA dehydrogenase (bHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and bHAD activity. Importantly, these mice are resistant to diet-induced obesity. Conclusions: This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.

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“…However, other neurally released substances besides catecholamines could also be involved in the regulation of lipolysis in obesity. For example, neuropeptide Y, which inhibits lipolysis (38), may modulate the catecholamine effect. Whether changes in the release of this or other neuromodulators could be relevant for the lipolytic resistance in obesity remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women.

et al. 2000

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Disturbed fat tissue metabolism with a reduction of the lipolytic rate could be an important pathogenetic factor in obesity. Lipolysis of the subcutaneous tissue of the thigh is partly under neural control and can be increased by intraneural stimulation of the lateral cutaneous femoral nerve in lean women. In the present study, we tested whether the lipolytic response to intraneural stimulation is altered in vivo in obese subjects. Seven obese women were examined and the results were compared with those of seven age-matched lean women. After an overnight fast, the lateral cutaneous femoral nerve was intraneurally stimulated for 10 min, and the local subcutaneous lipolytic response to this procedure was evaluated with microdialytic measurements of interstitial glycerol concentrations in the receptive field of the stimulated nerve fascicle. To exclude unspecific effects of stimulation, lipolysis was also controlled in a corresponding area of the contralateral leg. Intraneural stimulation produced no significant change in subcutaneous lipolysis in obese women (25.7 ± 9.7%, NS). This finding is in sharp contrast with the marked regional lipolytic response in lean women in which the same stimulation procedure enhanced the regional interstitial glycerol levels by 72 ± 17% (P < 0.05) compared with the unstimulated corresponding area of the contralateral leg. These in vivo results suggest that human obesity is characterized by a profound unresponsiveness of the subcutaneous adipose tissue to neurally stimulated lipolysis. This could be an important factor in the development and treatment of obesity. Diabetes 49:1875-1879, 2000 T he pathogenesis of obesity has been suggested to be intimately linked to the catecholaminergic regulation of lipolysis and the function of the sympathetic nervous system (1-3). Norepinephrine and epinephrine activate lipolysis via ␤ 1 -, ␤ 2 -, and ␤ 3 -adrenoceptors and inhibit it via ␣ 2 -adrenoceptors, and these neurotransmitters are the most important lipolytic substances in vivo (4). Defects of catecholamine-induced lipolysis have been observed in a number of obese subjects, and polymorphisms of the ␤ 2 -(5) and ␤ 3 -receptors (6) were suggested as explanations for this observation.The importance of sympathetic innervation of fat tissue is underlined by the observation that the recently described weight-regulating hormones, leptin (7), and the proopiomelanocorticotropin-derivate ␣-MSH (8) not only reduce appetite but also induce sympathoexcitation via the central nervous system. The relevance of such effects is obvious for the metabolically highly active brown adipose tissue in rats, which is densely innervated by sympathetic nerves directly controlled by autonomic brain stem centers (9-11). By comparison, the innervation of white adipose tissue (WAT) is sparse (12), and its role in regulating fat tissue metabolism is ill defined in humans (9,13). Recent studies from our laboratory on subjects with spinal cord injuries suggested that the neural control of basal WAT lipolysis appears to be i...

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Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

Cited by 78 publications

References 19 publications

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women.

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