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Leptin and adiponectin are two adipokines currently used as biomarkers for diagnostic orientation and phenotyping in syndromes of lipodystrophy and severe insulin resistance. The level of these biomarkers also has an impact on the therapeutic management of the patients. These aspects, as well as our experience as a reference center, are described in this brief overview.

The identification of leptin allowed the discovery of a new endocrine system. This major adipokine controlling energy homeostasis is also involved in the regulation of neuroendocrine function and fertility. Unfortunately, leptin is not able to treat common obesity, which associates hyperleptinemia and resistance to the hormone. Conversely, treatment with recombinant leptin is effective in situations of leptin deficiency. Several pathophysiological situations associated with adipose tissue dysfunctions and abnormal regulation of leptin secretion are discussed in this review. The advantage of the potential use of the leptin assay in some pathophysiological conditions is proposed.

Leptin and adiponectin are two adipokines. Their circulating concentrations, high for leptin and low for adiponectin, are predictive of insulin resistance and of an unfavorable cardiometabolic evolution in patients with obesity, metabolic syndrome or type 2 diabetes. In addition, recently, the adiponectin/leptin ratio has been proposed as an index of adipose tissue dysfunction together with threshold values for cardiometabolic risk for this index. The relevance and potential applications of the adiponectin/leptin and leptin/adiponectin ratios are discussed in the light of recent literature in this brief update.

Elevated circulating leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of leptin depending on the pathophysiological context. Studies performed in mice deficient in leptin or in leptin receptors are often contradictory, showing both protective and deleterious effects of leptin. These effects appear to vary depending on the genetic background of the animal and the doses of leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile. Adiponectin exerts protective effects at all stages of development of atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of adipokines actions and show the complexity to use these biomarkers in cardiovascular diseases. Resistance to the action of these adipokines is one of the hypotheses put forward to explain these discrepancies.

Context: Glucocorticoid therapy may result in adipose tissue redistribution of unknown pathophysiology., Objectives: To evaluate the effects of glucocorticoids on adipokine levels and adipose tissue inflammation. To compare the results in patients with or without glucocorticoid-induced lipodystrophy (GIL) after 3 months of therapy., Design and Setting: Prospective monocentric study., Patients: Adult patients initiating systemic, high-dose prednisone therapy for at least 3 months. Blood samples and subcutaneous abdominal adipose tissue biopsies were collected at baseline and month 3. The presence of GIL after 3 months of therapy was assessed using standardized photography., Results: Thirty-two patients were enrolled. Blood samples and subcutaneous abdominal adipose tissue were available at baseline and month 3 for 30 patients [median age: 61 (38-79) years, 77% women]. Among those 30 patients, 15 were classified as GIL+ and 15 were GIL- at month 3. Between baseline and month 3, adiponectin and leptin levels increased in the overall population while the level of resistin remained unchanged. At baseline, leptin level was higher [19.3 (8.3-31.1) vs 4.5 (2.4-11.3) μg/l, P = 0.006] and resistin level lower [7.1 (6.3-12.4) vs 10.4 (8.0-21.7) μg/l, P = 0.05] in GIL+ than in GIL- patients. Baseline leptin level was predictive of GIL occurrence. Receiver operating characteristic curve analysis demonstrated that the best diagnostic accuracy was obtained with a baseline leptin cut-off of 5.9 μg/l (sensitivity: 93%, specificity: 60%). At month 3, leptin and adiponectin levels increased more in the GIL+ than in the GIL- group, as did the number of anti-inflammatory M2 macrophages in subcutaneous abdominal fat., Conclusion: Glucocorticoid-induced lipodystrophy is associated with a different adipokine profile both before and after glucocorticoid therapy. Serum leptin level prior to glucocorticoid therapy is highly predictive of GIL occurrence., (© 2012 Blackwell Publishing Ltd.)

Two years ago, the Lasker Award was shared by Douglas Coleman and Jeffrey Friedman for their discovery of leptin, a hormone that exerts a key role in the central regulation of appetite and body weight. Douglas Coleman is recognized as the researcher who raised the hypothesis and predicted that a circulating satiety factor was lacking in the ob/ob mouse, and predicted that this factor acted at the hypothalamic level to modulate food intake. After three decades, in an attempt to identify the genes that were mutated in the ob/ob mouse, Jeffrey Friedman found that the ob gene encodes a protein hormone that reverses obesity and other abnormalities of this genetic rodent model of obesity. This discovery was a landmark event in physiology, and revolutionized our understanding of energy homeostasis. This short review aims to summarize the main steps that lead to the identification of leptin, the product of the ob gene., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: Insulin resistance and type 2 diabetes (T2D) are commonly seen in human immunodeficiency virus (HIV) infection and are related to antiretroviral therapy. Adiponectin and leptin secreted by adipocytes are both linked to body-fat distribution and insulin sensitivity. The present study aimed to assess the prevalence of insulin resistance and T2D, and their association with adiponectin and leptin, in Afro-Caribbean men and women with HIV infection., Methods: This cross-sectional study was conducted in an unselected sample of 237 HIV-1-infected patients. Clinical and metabolic parameters were measured, including fasting and postload plasma insulin, and circulating adiponectin and leptin levels. Insulin resistance was estimated by homoeostasis model assessment (HOMA-IR). Adjusted multiple logistic regressions were used to estimate the association of insulin resistance with adipokine levels and patients' characteristics., Results: A total of 132 men (mean age: 49 years) and 105 women (mean age: 48 years) were included in the study. Prevalences of T2D and insulin resistance were higher in women than in men [16.2% vs 8.3% (P = 0.06) and 24% vs 9.9% (P < 10⁻³), respectively]. Abdominal obesity was found in 47% of women and in 7% of men (P < 10⁻⁴). Insulin resistance was independently associated with adiponectin in women and with leptin in men., Conclusion: Insulin resistance is frequent in Afro-Caribbean women with HIV infection. Overweight and obesity are major risk factors in such a population. Systematic screening for insulin resistance should be carried out in this population, which has a high prevalence of T2D., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background & Aims: Mechanisms linking obesity and unfavourable outcomes in patients with viral hepatitis C (HCV) cirrhosis are not well understood. Obesity is associated with insulin resistance, increased leptin, and decreased adiponectin serum levels., Methods: We assessed the predictive value of those factors for the occurrence of hepatocellular carcinoma (HCC) and liver-related death or transplantation in a cohort of 248 patients (mean age 58 (12 years, BMI 25.4 ± 4.4 kg/m(2)) with compensated HCV cirrhosis and persistent infection prospectively followed and screened for HCC., Results: The mean baseline serum levels of adiponectin and leptin were 16.8 ± 15 mg/L and 16.8 ± 19 ng/ml, respectively. The mean homeostasis model assessment of insulin resistance (HOMA) index was 3.8 ± 3; median 2.9. After a median follow-up of 72 months, 61 patients developed HCC, 58 died of liver causes, and 17 were transplanted. The incidences (Kaplan Meier) of HCC were 7%, 18%, and 27% at 5 years (p=0.017) and of liver-related death or transplantation 15%, 15% and 29% (p=0.002) according to the lowest, middle and highest tertile of HOMA, respectively. In multivariate analysis, the HOMA index was associated with HCC occurrence (HR=1.10, [1.01-1.21] p=0.026) and was a strong predictor of liver-related death or transplantation (HR=1.13, [1.07-1.21] p<0.0001). Serum levels of adiponectin and leptin were not associated with the outcome., Conclusions: In patients with compensated HCV cirrhosis, insulin resistance but not serum levels of adiponectin and leptin predicted the occurrence of HCC and of liver-related death or transplantation., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients with non-alcoholic fatty liver disease (NAFLD)., Patients and Methods: Fifty-seven patients with biopsy-proven non-alcoholic steatohepatitis (NASH) (mean age 51+/-12, sex ratio 1), 17 with simple steatosis (mean age 47+/-12, sex ratio 1.4) and 10 controls without steatosis (mean age 51+/-11, sex ratio 4) were investigated. In all subjects, serum concentrations of triglycerides, ultrasensitive C reactive protein, leptin, adiponectin, soluble tumour necrosis factor receptor 1, interleukin (IL)-6 and Homeostasis Model Assessment Method (HOMA) were measured. Hepatic expression of adiponectin and its two receptors was assessed by quantitative reverse transcriptase polymerase chain reaction., Results: Body mass index (BMI) and HOMA were correlated positively with leptin levels (r=0.44 and 0.28 respectively) and negatively with the A/L ratio (r=0.51 and 0.41 respectively). Independent parameters associated with NASH vs steatosis were HOMA>3 [odds ratio (OR)=6.9] and A/L ratio <1.4 10(3) (OR=5.2). The combination of HOMA with A/L ratio showed an area under the receiver operating characteristic curve of 0.82 for distinguishing between NASH and steatosis. Extensive portal fibrosis was present in 17 (23%) patients with NAFLD. Three independent parameters were associated with fibrosis: age (OR=1.1), BMI (OR=1.3) and high IL-6 levels (OR=1.6). The hepatic expression of adiponectin receptor 2 was significantly higher in patients with NASH compared with controls and was related with necroinflammatory injury., Conclusions: This study shows that in patients with NAFLD, the combination of HOMA with A/L ratio may be a useful non-invasive approach to appreciate the severity of liver damage.

Recently, we characterized tumor suppressor candidate 5 (Tusc5) as an adipocyte-neuron PPARgamma target gene. Our objective herein was to identify additional genes that display distinctly high expression in fat and neurons, because such a pattern could signal previously uncharacterized functional pathways shared in these disparate tissues. gamma-Synuclein, a marker of peripheral and select central nervous system neurons, was strongly expressed in white adipose tissue (WAT) and peripheral nervous system ganglia using bioinformatics and quantitative PCR approaches. Gamma-synuclein expression was determined during adipogenesis and in subcutaneous (SC) and visceral adipose tissue (VAT) from obese and nonobese humans. Gamma-synuclein mRNA increased from trace levels in preadipocytes to high levels in mature 3T3-L1 adipocytes and decreased approximately 50% following treatment with the PPARgamma agonist GW1929 (P < 0.01). Because gamma-synuclein limits growth arrest and is implicated in cancer progression in nonadipocytes, we suspected that expression would be increased in situations where WAT plasticity/adipocyte turnover are engaged. Consistent with this postulate, human WAT gamma-synuclein mRNA levels consistently increased in obesity and were higher in SC than in VAT; i.e. they increased approximately 1.7-fold in obese Pima Indian adipocytes (P = 0.003) and approximately 2-fold in SC and VAT of other obese cohorts relative to nonobese subjects. Expression correlated with leptin transcript levels in human SC and VAT (r = 0.887; P < 0.0001; n = 44). Gamma-synuclein protein was observed in rodent and human WAT but not in negative control liver. These results are consistent with the hypothesis that gamma-synuclein plays an important role in adipocyte physiology.

Objective: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines., Subjects: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated., Method: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay., Results: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount., Conclusion: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.