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H Vidal

Publications and source records attributed to H Vidal.

At least 37 records · Page 2Linked to original sources
PubMed2003

Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity.

The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.

Adipose Tissue↗
PubMed2003

What kind of simple fasting index should be used to estimate insulin sensitivity in humans?

The hyperinsulinemic euglycemic glucose clamp method is the gold standard for measuring insulin resistance. However it is complex, and simple indexes have been developed. Some of them are based on formulae that calculate the product or the addition of fasting plasma insulin and glucose values whereas others are based on their ratios. We calculated several simple indexes of insulin resistance and compared them to hyperinsulinemic euglycemic clamp data in 111 subjects with a wide range of insulin resistance. We showed that indexes using insulin and glucose ratios in their formulae are poorly correlated with clamp measurements and give false evaluations, particularly in glucose-intolerant and type 2 diabetic subjects. Thus, whatever the glucose profile of study subjects, we suggest the use of a simple index based on the product or the addition of fasting plasma insulin and glucose values instead of their ratios to obtain insulin resistance evaluations close to the hyperinsulinemic euglycemic clamp technique.

Blood Glucose↗
PubMed2003

Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue of massively obese subjects.

The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue. Adipose tissue samples were collected from 30 massively obese subjects (10 men and 20 women) from omental, sc abdominal, and femoral depots. The mRNA expression of PPARgamma1, PPARgamma2, lipoprotein lipase, p85alpha phosphatidylinositol 3-kinase, and uncoupling protein 2 were quantified by reverse transcription-competitive PCR. The genotypes of Pro12Ala polymorphism were determined by single-strand conformation polymorphism analysis. The frequency of the Ala12 allele was 13.3% (8 Pro12Ala and 22 Pro12Pro). There were no differences in body weight, fat mass, and fasting serum leptin between the genotypes. The mRNA expression of p85alpha phosphatidylinositol 3-kinase was significantly lower in the omental fat of the Pro12Ala carriers than the Pro12Pro carriers (P < 0.01). It also appeared that PPARgamma2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPARgamma splice variants was lower in omental than sc fat independently of the genotype (P < 0.05-0.01). The common Pro12Ala polymorphism of the PPARgamma2 gene has minor influence on mRNA expression of PPARgamma target genes in adipose tissue of obese subjects. Expression of both PPARgamma splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.

Adipose Tissue↗
PubMed2003

[Obesity and inflammation: the adipocytokines].

It is now well documented that obesity is associated with a chronic, low grade, inflammatory state. The serum concentrations of a number of inflammatory markers, such as CRP, fibrinogene or serum amyloids are increased in obese subjects. More importantly, the levels of several pro-inflammatory cytokines, including TNFalpha, IL-6 and leptin are significantly higher in the plasma of obese patients. We will review here the possible role of adipose tissue and the production of adipocyte-derived cytokines in this inflammatory state. The observed increase in the concentrations of these adipocytokines is now suspected to play a determinant role in the development of most of the complications of obesity.

Adipose Tissue↗
PubMed2002

Hormone sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss.

OBJECTIVE: The effect of weight reduction on hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) gene expression and their relationship with adipose tissue metabolism were studied in massively obese men and women. SUBJECTS: Seventeen obese subjects (eight men, nine women) participated in the study (age 44+/-2 y, weight 145+/-8 kg, fat 40+/-2% of body mass, mean+/-s.e.m.), who were going through a gastric-banding operation for weight reduction. MEASUREMENTS: HSL and LPL mRNA expressions were analyzed using the reverse transcription competitive polymerase chain reaction. Subcutaneous fat lipolysis was measured in vivo by microdialysis and in vitro in isolated subcutaneous abdominal adipocytes. Measurements were done before and after 1 y of weight reduction. RESULTS: Significant reductions in weight (for men -20.3+/-2.5%, for women -18.3+/-2.1% (mean+/-s.e.m.) and fat mass (for men -27.6+/-7.9%, for women -21.8+/-3.9%) were observed in both genders. In women HSL mRNA expression decreased by 31% (P=0.008) and LPL expression increased slightly, but nonsignificantly (42%, P=0.110). These changes were not observed in men. In men, inhibition of lipolysis with alpha(2)-adrenergic and adenosine agonist was improved (P=0.001) in isolated adipocytes. CONCLUSIONS: This study uncovers new differences between genders in adipocyte metabolism along with weight reduction. In women, the observed changes in HSL and LPL gene expression suggest that deposition of lipids into adipose tissue might be favored after weight reduction. In men, the results indicate improved responsiveness to inhibition in adipose tissue metabolism along with weight reduction.

Adipocytes↗
PubMed2002

Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor.

BACKGROUND: In order to maintain body weight regulation, leptin directly or indirectly signals nutritional changes to key organs, but little is known about its target genes in human adipose tissue. Leptin receptor loss of function is a unique way to explore the role of leptin in the regulation of adipose tissue. OBJECTIVE: We studied the consequences of the absence of leptin signaling on adipocyte gene expression in two girls with a mutation in the leptin receptor. The expression levels of the ob gene and adipocyte transcription factors (SREBP1c, C/EPBalpha, beta, PPARgamma1, gamma2) were quantified by RT-PCR in subcutaneous adipose tissue of these patients and of 10 morbidly obese women. RESULTS: Ob mRNA levels in subjects lacking the leptin receptor were not overexpressed but were in the range that could be expected from their BMI (58 and 26 amol/ micro g total mRNA, range in obese women: 26-69). Expression of the five transcription factors was also in the same range in the affected patients and in morbidly obese women (7.7 and 6.8 amol/ micro g total mRNA, range: 2.2-9.4 for SREBP1c, 159 and 51 range: 51-406 for C/EPBalpha, 6.1 and 3.3 range: 2.4-24.8 for C/EPBbeta, 16.7 and 27.4 range: 9.4-29.7 for PPARgamma1 and 1.7 and 5.4 amol/ micro g total mRNA range: 1.7-8.8 for PPARgamma2). Significant correlation was found between the mRNA levels of leptin and PPARgamma2 and leptin and C/EBPalpha whereas no correlation was observed between leptin and SREBP1c, PPARgamma1, or C/EBPbeta mRNA levels. CONCLUSION: In patients lacking leptin signaling, the fact that ob gene expression is adequately adapted to their body fat mass argues against a direct negative feedback loop in the regulation of leptin expression in humans. The normal expression of several transcription factors, known to be dependent of the nutritional status, suggests that leptin is not a major contributor of their in vivo transcriptional regulation in human adipose tissue.

Adipocytes↗
PubMed2002

Molecular mechanisms of insulin-stimulated glucose uptake in adipocytes.

The stimulation of muscle and adipose tissue glucose metabolism, which is ultimately responsible for bringing about post-absorptive blood glucose clearance, is the primary clinically relevant action of insulin. Insulin acts on many steps of glucose metabolism, but one of the most important effects is its ability to increase the rate of cellular glucose transport. This results from the translocation of the insulin-responsive transporter isoform, GLUT4, from intra-cellular vesicular storage sites to the plasma membrane. In adipocytes, a substantial amount of cellular GLUT4 is located in a specific highly insulin-responsive storage pool, termed GLUT4 Storage Vesicles (GSVs). GLUT4 can also translocate to the plasma membrane from the recycling endosomal pool which also additionally contains the GLUT1 isoform of glucose transporter and the transferrin receptor. In this article we review the molecular mechanism by which insulin stimulates GLUT4 translocation in adipose cells, including the nature of the signaling pathways involved and the role of the cytoskeleton.

Adipocytes↗
PubMed2001

Expression of the splice variants of the p85alpha regulatory subunit of phosphoinositide 3-kinase in muscle and adipose tissue of healthy subjects and type 2 diabetic patients.

The regulation by insulin of the expression of the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase) is impaired in skeletal muscle and adipose tissue of type 2 diabetic patients. The gene encoding p85alpha (named grb-1) can generate several variants by alternative splicing, all being able to activate the p110 catalytic subunits of PI 3-kinase. Our aims were (i) to determine the mRNA expression profiles of these variants in human skeletal muscle and adipose tissue; (ii) to investigate the effect of insulin on their expression in vivo and in vitro in muscle and (iii) to verify whether this regulation is defective in type 2 diabetes. We determined the human genomic organization of grb-1 and set up reverse transcriptase competitive PCR assays for the quantification of each mRNA variant. In muscle, p85alpha and p50alpha mRNAs were the most abundant, and p55alpha represented less than 20% of all grb-1-derived mRNAs. In adipose tissue, p85alpha was expressed predominantly and p55alpha mRNA was not detectable. These expression profiles were not different in type 2 diabetics. During a 3 h hyperinsulinaemic clamp, insulin increased the mRNA expression of the three variants in muscle of control subjects. In diabetic patients, the effect of insulin on p85alpha and p50alpha mRNAs was blunted, and largely reduced on p55alpha transcripts. In cultured human myotubes, up-regulation of p85alpha, p55alpha and p50alpha mRNAs by insulin was abolished by LY294002 (10 microM) and by rapamycin (50 nM), suggesting that the PI 3-kinase/protein kinase B/p70 S6 kinase pathway could be involved in the stimulation of grb-1 gene expression by insulin in human muscle cells.

Adipose Tissue↗
PubMed2001

Nutritionally induced changes in the peroxisome proliferator-activated receptor-alpha gene expression in liver of suckling rats are dependent on insulinaemia.

It was previously found that the expression of peroxisome proliferator-activated receptor-alpha (PPARalpha) was markedly augmented in the liver of suckling rats, in comparison to the fetuses and most notably to adult rats and it paralleled similar changes in hepatic lipid concentration. To determine whether these changes could be related to the high lipid content of the maternal milk and/or to hormonal status, the role of changes in nutrient availability and in plasma insulin concentration on liver expression during the perinatal stage in vivo in the rat was studied. When suckling rats were weaned on day 17, instead of on day 20, the level of hepatic PPARalpha mRNA decreased earlier than in rats weaned later. When 10-day-old rats were force-fed with either glucose or Intralipid or a combination of both diets, it was found that, at similar low levels of plasma insulin, a high level of FFA stimulated PPARalpha expression, whereas, at similar high plasma FFA concentrations, an elevated insulin level attenuated the increase in PPARalpha expression. It is proposed that both the high lipid intake and decreased plasma insulin level are responsible for the high PPARalpha expression detected in rat neonates.

Acyl-CoA Oxidase↗
PubMed2001

Regulation of p85alpha phosphatidylinositol-3-kinase expression by peroxisome proliferator-activated receptors (PPARs) in human muscle cells.

Regulation of p85a phosphatidylinositol-3-kinase (p85alphaPI-3K) expression by peroxisome proliferator-activated receptor (PPAR) activators was studied in human skeletal muscle cells. Activation of PPARgamma or PPARbeta did not modify the expression of p85alphaPI-3K. In contrast, activation of PPARalpha increased p85alphaPI-3K mRNA. This effect was potentiated by 9-cis-retinoic acid, an activator of RXR. Up-regulation of p85alphaPI-3K gene expression resulted in a rise in p85alphaPI-3K protein level and in an increase in insulin-induced PI3-kinase activity. According to the role of p85alphaPI-3K in insulin action, these results suggest that drugs with dual action on both PPARgamma and PPARalpha can be of interest for the treatment of insulin resistance.

Alitretinoin↗
PubMed2001

15-deoxy-Delta 12,14-prostaglandin J2 induces apoptosis of human hepatic myofibroblasts. A pathway involving oxidative stress independently of peroxisome-proliferator-activated receptors.

Hepatic myofibroblasts (hMFs) play a key role in the development of liver fibrosis associated with chronic liver diseases. Apoptosis of these cells is emerging as a key process in the resolution of liver fibrosis. Here, we examined the effects of cyclopentenone prostaglandins on apoptosis of human hMFs. Cyclopentenone prostaglandins of the J series markedly reduced hMF viability, with 15-deoxy-Delta(12,14)-prostaglandin J2 (15-d-PGJ2) being the most potent. This effect was independent of peroxisome-proliferator-activated receptors (PPARs), because PPARgamma and PPARalpha agonists did not affect hMF cell viability, and PPARgamma, the nuclear receptor for 15-d-PGJ2, was not expressed in hMFs. Moreover, 15-d-PGJ2 did not act via a cell surface G protein-coupled receptor, as shown in guanosine-5'-O-(3-thiotriphosphate) binding assays. Cell death resulted from an apoptotic process, because 15-d-PGJ2-treated hMFs exhibited condensed nuclei, fragmented DNA, and elevated caspase-3 activity. Moreover, the caspase inhibitor Z-Val-Ala-Asp(OCH3)-fluoromethyl ketone blocked the cytotoxic effect of 15-d-PGJ2. The apoptotic effects of 15-d-PGJ2 were reproduced by H2O2 and blocked by the antioxidants N-acetylcysteine (NAC), N-(2-mercapto-propionyl)-glycine (NMPG) and pyrrolidine dithiocarbamate (PDTC). Accordingly, 15-d-PGJ2 generated rapid production of reactive oxygen species in hMFs, via a NAC/NMPG/PDTC-sensitive pathway. In conclusion, 15-d-PGJ2 induces apoptosis of human hMFs via a novel mechanism involving oxidative stress and unrelated to activation of its nuclear receptor PPARgamma. These data underline the antifibrogenic potential of 15-d-PGJ2.

Apoptosis↗
PubMed2001

The regulation of uncoupling protein-2 gene expression by omega-6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor beta.

Fatty acids have been postulated to regulate uncoupling protein (UCP) gene expression in skeletal muscle in vivo. We have identified, at least in part, the mechanism by which polyunsaturated fatty acids increase UCP-2 expression in primary culture of human muscle cells. omega-6 fatty acids and arachidonic acid induced a 3-fold rise in UCP-2 mRNA levels possibly through transcriptional activation. This effect was prevented by indomethacin and mimicked by prostaglandin (PG) E(2) and carbaprostacyclin PGI(2), consistent with a cyclooxygenase-mediated process. Incubation of myotubes for 6 h with 100 micrometer arachidonic acid resulted in a 150-fold increase in PGE(2) and a 15-fold increase in PGI(2) in the culture medium. Consistent with a role of cAMP and protein kinase A, both prostaglandins induced a marked accumulation of cAMP in human myotubes, and forskolin reproduced the effect of arachidonic acid on UCP-2 mRNA expression. Inhibition of protein kinase A with H-89 suppressed the effect of PGE(2), whereas cPGI(2) and arachidonic acid were still able to increase ucp-2 gene expression, suggesting additional mechanisms. We found, however, that the MAP kinase pathway was not involved. Prostaglandins, particularly PGI(2), are potent activators of the peroxisome proliferator-activated receptors. A specific agonist of peroxisome proliferator-activated receptor (PPAR) beta (L165041) increased UCP-2 mRNA levels in myotubes, whereas activation of PPARalpha or PPARgamma was ineffective. These results suggest thus that ucp-2 gene expression is regulated by omega-6 fatty acids in human muscle cells through mechanisms involving at least protein kinase A and the nuclear receptor PPARbeta.

Cyclic AMP-Dependent Protein Kinases↗
PubMed2001

The expression of the p85alpha subunit of phosphatidylinositol 3-kinase is induced by activation of the peroxisome proliferator-activated receptor gamma in human adipocytes.

AIMS/HYPOTHESIS: Thiazolidinediones are new oral antidiabetic drugs that activate the nuclear receptor PPARgamma. Our aim was to identify potential target genes of PPARgamma in the human adipocyte in order to clarify how thiazolidinediones improve insulin sensitivity. METHODS: The effect of BRL 49653 (Rosiglitazone) on the mRNA expression of insulin receptor, insulin receptor substrate-1, p85alpha, p110alpha and p110beta subunits of phosphatidylinositol 3-kinase, Glut 4 and hormone sensitive lipase was examined in isolated adipocytes. Target mRNA levels were determined by RT-competitive PCR. RESULTS: The BRL 49653 (1 micromol/l) increased the mRNA concentrations of p85alphaPI-3 K (264 +/- 46 vs 161 +/- 31 amol/microg total RNA, p = 0.003) whithout affecting the expression of the other mRNAs of interest. This effect was dose-dependent (K0.5 = 5 nmol/l) and was reproduced by a specific activator of RXR, indicating that it was probably mediated by the PPARgamma/RXR heterodimer. The BRL 49653 also increased the amount of p85alphaPI-3K protein in adipose tissue explants (71 +/- 19%). In addition, BRL 49653 produced a more than twofold increase in insulin stimulation of phosphatidylinositol 3-kinase activity and significantly enhanced the antilipolytic action of insulin. CONCLUSION/INTERPRETATION: This work demonstrates that the gene of p85alphaPI-3K is probably a target of PPARgamma and that thiazolidinediones can improve insulin action in normal human adipocytes. Although the precise mechanism of action of BRL 49653 on PI3-Kinase activity is not completely clear, these findings improve our understanding of the insulin-sensitizing effects of the thiazolidinediones, possible drugs for the treatment of Type II (non-insulin-dependent) diabetes mellitus.

Adipocytes↗
PubMed2001

Sterol regulatory element binding protein 1c (SREBP-1c) expression in human obesity.

OBJECTIVE: Investigation of the expression of sterol regulatory element binding protein-1c (SREBP-1c) in different adipose tissue depots in morbidly obese subjects before and after 1 year of weight loss induced by gastric banding operation. RESEARCH METHODS AND PROCEDURES: SREBP-1c expression was studied in 20 massively obese subjects (6 men and 14 women; age: 41 +/- 9 years; weight: 148 +/- 34 kg; percentage of body fat: 42 +/- 4; mean +/- SD) using reverse transcription competitive polymerase chain reaction. Adipose tissue biopsies were taken from omental, subcutaneous abdominal, and femoral depots before weight loss, and from subcutaneous depots after weight loss. Subcutaneous samples were taken also from 6 normal weight subjects. RESULTS: The level of SREBP-1c mRNA was significantly lower in omental (1.8 +/- 0.2 amol/microg of total RNA) than in subcutaneous abdominal (3.7 +/- 0.4 amol/microg of total RNA) or femoral (3.9 +/- 0.4 amol/microg of total RNA; p < 0.001, mean +/- SEM) depots. The values in subcutaneous depots were about twice as high in normal weight (7.4 +/- 2.5 for abdominal and 6.5 +/- 1.5 for femoral, p < 0.01) as in obese subjects. After weight loss, the mRNA levels of SREBP-1c increased in obese subjects, both in subcutaneous abdominal (5.3 +/- 0.7, p < 0.01) and in femoral (4.8 +/- 0.8, p < 0.05) tissue. DISCUSSION: SREBP-1c mRNA expression was lower in omental adipose tissue than in subcutaneous depots in obese subjects before weight loss. Furthermore, the expression of SREBP-1c in obese subjects was clearly lower than in normal weight subjects, but mRNA levels increased along with weight reduction. Weight reduction was associated with increased mRNA levels of SREBP-1c in obese subjects. The reduced expression of SREBP-1c in obesity could be ascribed to lowered action or concentration of insulin, changeable along with weight reduction. However, changes in SREBP-1c expression after weight reduction could also be ascribed to the changes in calorie intake or nutritional habits after gastric banding operation.

Abdomen↗
PubMed2001

Plasma acylation stimulating protein concentration and subcutaneous adipose tissue C3 mRNA expression in nondiabetic and type 2 diabetic men.

We studied the effect of an oral fat load on plasma acylation stimulating protein (ASP) concentrations in 9 lean healthy (age 59+/-2 years, body mass index [BMI] 23.2+/-0.4 kg/m(2); both mean+/-SEM), 9 obese nondiabetic (58+/-2 years, BMI 29.4+/-0.5 kg/m(2)), and 12 type 2 diabetic (60+/-2 years, BMI 29.6+/-1.0 kg/m(2)) men. Because ASP is a cleavage product of complement protein C3 (C3adesArg) and its secretion is regulated by insulin, we also examined the subcutaneous adipose tissue expression of C3 mRNA before and after a 240-minute euglycemic hyperinsulinemic clamp in a subgroup of these men. Plasma ASP concentration and adipose tissue C3 mRNA expression were higher in the obese groups than in the lean men. Plasma ASP concentration did not change significantly after the fat load. Fasting plasma ASP concentration and C3 mRNA expression were correlated negatively with insulin sensitivity and positively with the magnitude of postprandial lipemia in nondiabetic but not in type 2 diabetic men. The expression of C3 mRNA was not regulated by insulin. These data suggest that ASP is associated with whole-body glucose and lipid metabolism in nondiabetic individuals, whereas metabolic disturbances in diabetes may overcome the regulatory role of ASP in lipid and glucose metabolism.

Adipose Tissue↗
PubMed2001

Age-related differences in messenger ribonucleic acid expression of key proteins involved in adipose cell differentiation and metabolism.

This study was performed to compare the expression of key proteins [lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), complement 3 (C3), and peroxisome proliferator-stimulated receptor-gamma (PPAR gamma)] involved in sc abdominal adipose tissue (AT) metabolism of young (n = 13) vs. middle-aged (n = 16) men. The sc abdominal AT-LPL activity as well as fat cell lipolysis were also measured in both groups of men. Young and middle-aged men displayed similar body weight and sc abdominal fat accumulation, measured by computed tomography. However, middle-aged men were characterized by a higher percent body fat (28 +/- 5% vs. 22 +/- 7%; P < 0.05) than young subjects. No difference between groups was observed in sc abdominal adipose tissue LPL activity. On the other hand, maximal lipolytic responses of sc abdominal adipocytes to isoproterenol (beta-adrenergic agonist) or to postadrenoceptor agents such as dibutyryl cAMP, forskolin, and theophylline were lower in middle-aged than in young men (P < 0.05). AT-LPL messenger ribonucleic acid (mRNA) levels were similar regardless of the subject's age. However, HSL, C3, and PPAR gamma mRNA levels were higher in middle-aged than in young individuals (P < 0.01-0.05). After correction for percent body fat, only HSL and C3 mRNA levels remained significantly different between groups (P < 0.05). Taken together, these results suggest that aging has an effect on the up-regulation of HSL and C3 mRNA levels, whereas PPAR gamma expression seems to be related mainly to increased adiposity.

Abdomen↗
PubMed2001

Prenatal leptin production: evidence that fetal adipose tissue produces leptin.

In the adult, circulating leptin is highly correlated to adipose tissue mass. Whether such a relationship exists prenatally is unknown, because the actual source of fetal leptin has not been determined. In the present study, we have assessed the placental contribution to fetal and maternal circulating leptin concentrations and determined whether fetal adipose tissue produces leptin. The rate of leptin production in dually perfused human placenta was 0.036 ng/min.g. Ninety-five percent of the leptin released was delivered into the maternal circulation, vs. only 5% on the fetal side. Leptin messenger RNA and protein were detected in adipose tissue biopsies of 20-38 week human fetuses. However, leptin concentration was twice lower in fetal (0.22 +/- 0.11 ng/mg protein, n = 6) than in adult (0.49 +/- 0.12 ng/mg protein, n = 8) adipose tissue. Umbilical leptin levels closely reflected ponderal index at birth over a wide range of birth weights (1.6--4.1 kg). In sharp contrast, maternal and placental leptin concentrations were increased in pregnancies associated with fetal growth retardation. We conclude that umbilical leptin levels are independent of placental leptin production and can be taken as a marker of fat mass in human fetuses. By contrast, placental leptin production makes a substantial contribution to maternal circulating leptin levels during pregnancy.

Adipose Tissue↗