Leptin resistance in obese humans: does it exist and what does it mean?

Arch, Jonathan R. S.; Stock, Michael J.; Trayhurn, Paul

doi:10.1038/sj.ijo.0800779

Cited by 64 publications

(44 citation statements)

References 40 publications

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“…34 As a consequence, the finding of high circulating leptin in subjects with overweight/obesity, 35 is strongly suggestive of a resistance to the physiological effect of the hormone. 36 Accordingly, a high correlation was recently found between the serum levels of leptin and its biological effect. 37 The finding of an endothelial dysfunction in subjects with the Metabolic Syndrome deserves further comments.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study

et al. 2003

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OBJECTIVES:The present study aimed at evaluating the prevalence of the Metabolic Syndrome and at identifying its additional clinical features. RESEARCH DESIGN AND METHODS: Within a prospective population-based survey examining 888 subjects aged 40-79 y, subjects were identified fulfilling the WHO and the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria for diagnosing the Metabolic Syndrome. In these subjects and in the rest of the sample (controls), several metabolic and nonmetabolic biochemical parameters were compared. RESULTS: The prevalence of the Metabolic Syndrome by WHO criteria was 34.1% (95% CI 31.0-37.2) and by NCEP-ATPIII criteria 17.8% (15.5-20.3). The prevalence was significantly higher in older subjects and in those less physically active. Subjects with the Metabolic Syndrome either by WHO or by NCEP-ATPIII criteria showed higher levels of oxidized low-density lipoprotein, apolipoprotein B, urate, leptin, fibrinogen, leukocytes, erythrocyte sedimentation rate, GOT, gamma-GT and soluble endothelial adhesion molecules (E-selectin, vascular adhesion molecule-1 and intercellular adhesion molecule-1) and lower apolipoprotein A concentrations. Insulin resistance, as assessed by the Homeostasis Model Assessment, increased with the increase in the number of traits composing the syndrome found within the single individual. Subjects with insulin resistance had more pronounced abnormalities in several parameters, including the additional features of the syndrome (eg fibrinogen and soluble adhesion molecules). CONCLUSIONS: The Metabolic Syndrome occurs very frequently in the general population aged 40-79 y, and is associated with several additional metabolic and nonmetabolic abnormalities that likely contribute to an increased cardiovascular risk. Insulin resistance seems to play a major role in classic and additional abnormalities featuring the Metabolic Syndrome.

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Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study

et al. 2003

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“…Synthesis and secretion of leptin is increased in most obese humans, and the plasma leptin level is correlated tightly with the percentage of body fat Maffei et al, 1995;Masuzaki et al, 1997). These observations strongly indicate the presence of leptin resistance in human obesity Heek et al, 1997;Arch et al, 1998;Beaufrere & Morio, 2000). In addition to the regulation associated with adipose tissue mass, leptin production is known to be regulated by such factors as peripheral nutritional status (Kolaczynski et al, 1996a,b;Boden et al, 1996;Reseland et al, 2001), sympathetic nerve activity (Auwerx & Staels, 1998;Slieker et al, 1996;Mantzoros et al, 1996), and a series of humoral factors (Auwerx & Staels, 1998).…”

Section: Introductionmentioning

confidence: 97%

Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

et al. 2002

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Objective: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. Design: Longitudinal study. Setting: University and foundation hospitals. Subjects: Ten obese men and 10 premenopausal obese women. Interventions: Five men and five women took 800 kcal=day LCD and another five men and five women took 1400 kcal=day balanced deficit diet (BDD) during 4 weeks. Results: Plasma leptin levels in the LCD group decreased more markedly (46.2 AE 14.6 to 13.2 AE 3.6 ng=ml) than that expected for the decrement in percentage fat (39.0 AE 1.7 to 35.9 AE 1.7%) and body mass index (BMI; 35.4 AE 2.4 to 33.1 AE 2.2 kg=m 2 ), while that in the BDD group did not decrease significantly (14.9 AE 3.5 to 13.4 AE 2.8 ng=ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5 AE 2.7 vs 29.3 AE 2.1%, P ¼ 0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r ¼ 0.586, P ¼ 0.0003) and T3 (r ¼ 0.785, P ¼ 0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r ¼ 0.928, P < 0.0001). The plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter. Conclusions: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity.

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“…Also, it cannot be shown that the isolated hypothalami of obese individuals respond poorly to leptin in the way that studies can be conducted on isolated adipose or muscle tissue from subjects with diabetes. Leptin levels might simply be raised in response to adiposity, just as insulin is raised in response to high blood glucose after a meal (Arch et al 1998). It is difficult to distinguish cause and effect in the case of obesity and leptin; subjects with diabetes can be studied in the fasted state, whereas the stimulus (adiposity) to leptin secretion in obese subjects is always present.…”

Section: Central Resistance To Leptin and Insulinmentioning

confidence: 99%

Central regulation of energy balance: inputs, outputs and leptin resistance

Arch

2005

Proc. Nutr. Soc.

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The regulation of energy balance is complex and, in man, imprecise. Nevertheless, in many individuals intake and expenditure are balanced with <1% error with little or no conscious effect. Essential components of such a regulatory system are signals, leptin and insulin, that reflect the size of lipid stores. Leptin receptors signal via phosphatidylinositol 3-kinase (as do insulin receptors) and via the transcription factor signal transducer and activator of transcription-3 to activate various types of neurone. Obese rodents, and possibly man, are resistant to leptin; in some cases because of genetic or perinatal programming (primary resistance), but commonly in response to high leptin levels (secondary resistance). Secondary leptin resistance may be a result of reduced transport of leptin to the brain or down-regulation of leptin signalling. Signals that reflect lipid stores form the tonic homeostatic regulatory system. They interact with episodic homeostatic signals carried by neurones, hormones and metabolites to regulate meal size and frequency. They also interact with signals related to the palatability of food, biorhythms and learning. Many neurotransmitters and hormones mediate responses to more than one input (e.g. gastric and adipocyte leptin), but are nevertheless most involved with particular inputs (e.g. leptin with adipocyte fat stores). Feeding can be divided into appetitive (preparation for feeding) and consummatory phases, which can both be further subdivided. Different sets of neurotransmitters and hormones are involved at each stage. In the long term it may be possible to customise obesity therapies according to those inputs and outputs that are most disturbed and most amenable to intervention in individual subjects.

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Leptin resistance in obese humans: does it exist and what does it mean?

Cited by 64 publications

References 40 publications

Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study

Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study

Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

Central regulation of energy balance: inputs, outputs and leptin resistance

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