Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease

Couillard, Charles; Mauriège, Pascale; Prud’homme, Denis; Nadeau, André; Tremblay, Angelo; Bouchard, Claude; Després, Jean‐Pierre

doi:10.1007/s001250050804

Cited by 132 publications

(96 citation statements)

References 46 publications

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“…As expected, the serum leptin level was significantly higher in women. Such a gender difference in serum leptin levels has been reported previously [14] . Leptin is exclusively expressed in adipose tissue and secreted from white adipose cells [15] .…”

Section: Discussionsupporting

confidence: 72%

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

Huang¹,

Fan²,

Hen³

et al. 2008

WJG

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feature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin. INTRODUCTIONLeptin -the ob gene product -is a circulating 16-kDa peptide hormone secreted mainly by adipocytes of white fat tissue. It regulates food intake, body fat, insulin action, thermogenesis, induction of angiogenesis, and modulation of the immune system. Leptin synthesis in adipocytes is regulated by several hormones [1] . Leptin action in peripheral tissues involves interaction with specific transmembrane receptors. The leptin receptor (Ob-R), which is a member of the class-1 cytokine receptor family, may be an important determinant of leptin sensitivity. Ob-R was originally demonstrated in hypothalamic neurons, through which leptin regulates food intake and body weight [2] . Alongside several membrane-bound isoforms of Ob-R, with varying cytoplasmic length and with the same extracellular domain, a soluble form of the leptin receptor (sOb-R) can be demonstrated. sOb-R represents the main leptin-binding compound in plasma, which results in fractions of bound and free leptin in plasma [3] . The balance between the free form, the rapidly bioavailable compartment, and bound leptin regulates leptin bioavailability [4] . However, the precise pathophysiological role of sOb-R has not yet been defined.Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a common and potentially severe condition often associated with obesity, type 2 diabetes and Abstract AIM:To determine the role of leptin system in non-alcoholic fatty liver disease (NAFLD) development by delineating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS:Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS:Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). There was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently related to serum leptin levels. CONCLUSION:Elevated serum leptin seems to be a

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Section: Discussionsupporting

confidence: 72%

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

Huang¹,

Fan²,

Hen³

et al. 2008

WJG

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“…21 In the present study, a gender difference in adipocyte size was found as women had Figure 1 Associations of abdominal fat cell weight (FCW; left panels) and femoral FCW (right panels), expressed in mg lipidacell, with plasma insulin (top panels) and leptin (bottom panels) concentrations in 63 men (black circles) and 42 women (white circles).…”

Section: Discussionmentioning

confidence: 51%

“…However, associations between femoral FCW and plasma insulin as well as leptin levels were only signi®cant in women. Since plasma leptin concentrations have not been reported to be associated with regional AT distribution, 21,26,54,55 we believe that the reduced AT accumulation in the femoral region in men may account for the absence of relationship found in our male subjects. Overall, our observations support the notion that fat cell size is an important correlate of leptinemia.…”

Section: Discussionmentioning

confidence: 63%

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia

Couillard¹,

et al. 2000

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OBJECTIVES: To investigate the relationships of fat cell weight (FCW) as well as of estimated total adipose cell number to fasting plasma leptin concentration. DESIGN: Cross-sectional correlational study. SUBJECTS: A sample of 63 men (mean age AE s.d.: 36 AE 4 y) and 42 premenopausal women (35 AE 5 y). MEASUREMENTS: Adipose tissue (AT) biopsies were obtained in order to determine FCW as well as estimated adipose cell number. Fasting plasma leptin and insulin concentrations as well as various fatness and body fat distribution variables (underwater weighing and computed tomography) were also measured. RESULTS: In both genders, mean FCW as well as the estimated adipose cell number were signi®cantly correlated with body fatness and AT distribution variables (0.41 r 0.84). Larger abdominal (P`0.005) and femoral (P`0.0001) FCW were found in women than in men. This gender difference in adipose cell size was associated with increased leptin concentrations in women compared with men. In both genders, increased abdominal FCW was associated with higher plasma leptin concentrations (men: r 0.38, P`0.005 and women: r 0.55, P`0.0001). However, the association between femoral FCW and leptinemia was only signi®cant in women (r 0.45, P`0.005). Contrary to women, plasma leptin concentrations were associated with estimated adipose cell number in men (r 0.59, P`0.0001). Multiple regression analyses revealed that gender (43.3%), mean FCW (16.2%) and the estimated adipose cell number (10.1%) were signi®cant predictors of fasting leptinemia. CONCLUSIONS: Results of the present study indicate that in men and women, adipose cell hypertrophy is associated with increased plasma leptin concentrations. This ®nding provides further support to the observation that adipose tissue leptin secretion may be regulated, at least to a certain extent, by adipocyte size. Thus, the present study suggests that the higher plasma leptin concentrations found in women than in men could be partly explained by the well documented gender difference in adipose cell size and number.

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“…12,23 In the fasting status, insulin injection can increase ob mRNA to levels of fed controls, 12,13 which suggests leptin mRNA expression is up-regulated by insulin. 59 However, leptin expression does not change after shortterm caloric restriction 19 and there is no acute insulin effect (either with euglycemic clamps, insulin injection or post-prandially) on ob gene mRNA expression or plasma leptin concentrations. 16 ± 21 Levels of leptin are increased by insulin only after prolonged administration; 2,12 a result consistent with our ®ndings that elevated HbA1c, and not c-peptide or insulin, is associated with higher leptin levels.…”

Section: Discussionmentioning

confidence: 99%

Glycemic status and soluble tumor necrosis factor receptor levels in relation to plasma leptin concentrations among normal weight and overweight US men

et al. 2000

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OBJECTIVE: Leptin, an adipocyte-derived protein product of the obesity (ob) gene, is a multifunctional polypeptide associated with the development of obesity-related disorders in humans. There is considerable inter-individual variation in plasma leptin even among subjects with comparable obesity levels, which suggests that factors other than adipose mass may be involved in the regulation of leptin expression andaor production. The purpose of this study was to evaluate the potential role of glycemic status and adipose-derived cytokines in regulating plasma leptin levels among normal and overweight men. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: We measured plasma leptin, insulin, c-peptide and plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Followup Study (HPFS), and aged 47 ± 64 y in 1994, were free of cardiovascular disease, diabetes mellitus, malignant neoplasms, and had provided a fasting blood sample and a detailed lifestyle questionnaire. RESULTS: Men in the highest quintile of plasma leptin (mean 12.7 ngaml) weighed more, were less physically active and had higher circulating insulin, c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quintile (mean 2.8 ngaml). We found a signi®cant correlation between plasma insulin, c-peptide, glycosylated hemoglobin (HbA1c), and sTNF-R1 on leptin concentrations (with Spearman correlation coef®cients ranging from 0.17 to 0.48 and all P`0.05). Only HbA1c and sTNF-R1 were independently and positively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these observed associations were limited to men with a BMI !25 kgam 2 . CONCLUSION: Our results suggest that glucose homeostasis and the activity of the TNF system may modulate leptin secretion and production among overweight men. Glucose homeostasis and TNF-a a is important in metabolic disorders related to hyperleptinemia.

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Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease

Cited by 132 publications

References 46 publications

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia

Glycemic status and soluble tumor necrosis factor receptor levels in relation to plasma leptin concentrations among normal weight and overweight US men

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