Ad libitum intake of a high-carbohydrate or high-fat diet in young men: effects on nutrient balances.

The effect of diet composition [high-carbohydrate, low-fat (HC) and high-fat, low-carbohydrate (HF) diets] on macronutrient intakes and nutrient balances was investigated in young men of normal body weight. Eleven subjects were studied on two occasions for 48 h in a whole-body indirect calorimeter in a crossover design. Subjects selected their meals from a list containing a large variety of common food, which had a food quotient > 0.85 for the HC diet and < 0.85 for the HF diet. The average ad libitum intake was 14.41 +/- 0.85 MJ/d (67%, 18%, and 15% of energy as carbohydrate, fat, and protein, respectively) with the HC diet and 18.25 +/- 0.90 MJ/d (26%, 61%, and 13% of energy as carbohydrate, fat, and protein, respectively) with the HF diet. Total energy expenditure was not significantly influenced by diet composition: 10.46 +/- 0.27 and 10.97 +/- 0.22 MJ/d for the HC and HF diets, respectively. During the 2 test days, cumulative carbohydrate storage was 418 +/- 72 and 205 +/- 47 g, and fat balance was 29 +/- 17 and 291 +/- 29 g with the HC and HF diets, respectively. Only the HF diet induced a significantly positive fat balance. These results emphasize the important role of the dietary fat content in body fat storage.

Ins1 (Cre) knock-in mice for beta cell-specific gene recombination.

AIMS/HYPOTHESIS: Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy of major forms of diabetes. Selective gene inactivation in pancreatic beta cells, using the Cre-lox system, is a powerful approach to assess the role of particular genes in beta cells and their impact on whole body glucose homeostasis. Several Cre recombinase (Cre) deleter mice have been established to allow inactivation of genes in beta cells, but many show non-specific recombination in other cell types, often in the brain. METHODS: We describe the generation of Ins1 (Cre) and Ins1 (CreERT2) mice in which the Cre or Cre-oestrogen receptor fusion protein (CreERT2) recombinases have been introduced at the initiation codon of the Ins1 gene. RESULTS: We show that Ins1 (Cre) mice induce efficient and selective recombination of floxed genes in beta cells from the time of birth, with no recombination in the central nervous system. These mice have normal body weight and glucose homeostasis. Furthermore, we show that tamoxifen treatment of adult Ins1 (CreERT2) mice crossed with Rosa26-tdTomato mice induces efficient recombination in beta cells. CONCLUSIONS/INTERPRETATION: These two strains of deleter mice are useful new resources to investigate the molecular physiology of pancreatic beta cells.

Evidence-based Economic Policy - Three Essays in Applied Microeconometrics

Over thirty years ago, Leamer (1983) - among many others - expressed doubts about the quality and usefulness of empirical analyses for the economic profession by stating that "hardly anyone takes data analyses seriously. Or perhaps more accurately, hardly anyone takes anyone else's data analyses seriously" (p.37). Improvements in data quality, more robust estimation methods and the evolution of better research designs seem to make that assertion no longer justifiable (see Angrist and Pischke (2010) for a recent response to Leamer's essay). The economic profes- sion and policy makers alike often rely on empirical evidence as a means to investigate policy relevant questions. The approach of using scientifically rigorous and systematic evidence to identify policies and programs that are capable of improving policy-relevant outcomes is known under the increasingly popular notion of evidence-based policy. Evidence-based economic policy often relies on randomized or quasi-natural experiments in order to identify causal effects of policies. These can require relatively strong assumptions or raise concerns of external validity. In the context of this thesis, potential concerns are for example endogeneity of policy reforms with respect to the business cycle in the first chapter, the trade-off between precision and bias in the regression-discontinuity setting in chapter 2 or non-representativeness of the sample due to self-selection in chapter 3. While the identification strategies are very useful to gain insights into the causal effects of specific policy questions, transforming the evidence into concrete policy conclusions can be challenging. Policy develop- ment should therefore rely on the systematic evidence of a whole body of research on a specific policy question rather than on a single analysis. In this sense, this thesis cannot and should not be viewed as a comprehensive analysis of specific policy issues but rather as a first step towards a better understanding of certain aspects of a policy question. The thesis applies new and innovative identification strategies to policy-relevant and topical questions in the fields of labor economics and behavioral environmental economics. Each chapter relies on a different identification strategy. In the first chapter, we employ a difference- in-differences approach to exploit the quasi-experimental change in the entitlement of the max- imum unemployment benefit duration to identify the medium-run effects of reduced benefit durations on post-unemployment outcomes. Shortening benefit duration carries a double- dividend: It generates fiscal benefits without deteriorating the quality of job-matches. On the contrary, shortened benefit durations improve medium-run earnings and employment possibly through containing the negative effects of skill depreciation or stigmatization. While the first chapter provides only indirect evidence on the underlying behavioral channels, in the second chapter I develop a novel approach that allows to learn about the relative impor- tance of the two key margins of job search - reservation wage choice and search effort. In the framework of a standard non-stationary job search model, I show how the exit rate from un- employment can be decomposed in a way that is informative on reservation wage movements over the unemployment spell. The empirical analysis relies on a sharp discontinuity in unem- ployment benefit entitlement, which can be exploited in a regression-discontinuity approach to identify the effects of extended benefit durations on unemployment and survivor functions. I find evidence that calls for an important role of reservation wage choices for job search be- havior. This can have direct implications for the optimal design of unemployment insurance policies. The third chapter - while thematically detached from the other chapters - addresses one of the major policy challenges of the 21st century: climate change and resource consumption. Many governments have recently put energy efficiency on top of their agendas. While pricing instru- ments aimed at regulating the energy demand have often been found to be short-lived and difficult to enforce politically, the focus of energy conservation programs has shifted towards behavioral approaches - such as provision of information or social norm feedback. The third chapter describes a randomized controlled field experiment in which we discuss the effective- ness of different types of feedback on residential electricity consumption. We find that detailed and real-time feedback caused persistent electricity reductions on the order of 3 to 5 % of daily electricity consumption. Also social norm information can generate substantial electricity sav- ings when designed appropriately. The findings suggest that behavioral approaches constitute effective and relatively cheap way of improving residential energy-efficiency.

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma.

We present the long-term results of 18 chemotherapy relapsed indolent (N = 12) or transformed (N = 6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, (131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.

Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia.

Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea level but train under hypoxic conditions, has gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic' or 'anaerobic' interval training, it is believed that IHT would potentiate greater performance improvements compared to similar training at sea level. A thorough analysis of studies including IHT, however, leads to strikingly poor benefits for sea-level performance improvement, compared to the same training method performed in normoxia. Despite the positive molecular adaptations observed after various IHT modalities, the characteristics of optimal training stimulus in hypoxia are still unclear and their functional translation in terms of whole-body performance enhancement is minimal. To overcome some of the inherent limitations of IHT (lower training stimulus due to hypoxia), recent studies have successfully investigated a new training method based on the repetition of short (<30 s) 'all-out' sprints with incomplete recoveries in hypoxia, the so-called repeated sprint training in hypoxia (RSH). The aims of the present review are therefore threefold: first, to summarise the main mechanisms for interval training and repeated sprint training in normoxia. Second, to critically analyse the results of the studies involving high-intensity exercises performed in hypoxia for sea-level performance enhancement by differentiating IHT and RSH. Third, to discuss the potential mechanisms underpinning the effectiveness of those methods, and their inherent limitations, along with the new research avenues surrounding this topic.

Biokinetics and dosimetry of 111 In-DOTA-NOC-ATE compared with 111In-DTPA-Octreotide

Aim: Biokinetics and dosimetry of 111In-DOTA-NOC-ATE (NOCATE) and 111In-DTPA-octreotide (Octreoscan?, OCTREO) were comparatively studied in the same patients. Patients and Methods: Seventeen patients (10 males, 7 females), mean age 60 years referred for an Octreoscan? because of carcinoid (N=9), unspecified neurodendocrine tumors (N=6), thymoma (N=1) or medullary thyroid carcinoma (N=1) accepted a second study with NOCATE. Four patients had no detectable tumor at the time of scanning. Whole-body (WB) anterior-posterior scans were recorded 0.5 (100% reference scan), 4, 24 and 48 hrs (N=17) and 120 hrs (N=6) after injection. OCTREO (178±15 MBq) preceded NOCATE (108±14 MBq) imaging with 16±5 days in 16 patients while 1 patient had first NOCATE followed 14 days later by OCTREO. Blood samples were taken 5, 15, 30, 60, 240 and 1440 min after injection. Background corrected geometric mean counts of WB, lung, kidney, liver, spleen and blood counts expressed in % of the initial composite WB and blood counts, respectively were fitted to bi- or single exponential curves and dosimetry was performed for male and female patients using MIRDOSE3.1 and OLINDA/EXM. Results: Initially, WB, lung and kidney activity was similar but retention was significantly higher for NOCATE compared with OCTREO. Liver and spleen uptake of NOCATE was higher from beginning (p<0.001) and remained so over time. Activity in rest of body showed similar α and β half-lives, but the β half-life fraction of NOCATE was much higher than OCTREO (49% vs. 19%, respectively). Blood T1/2β was longer for NOCATE compared with OCTREO (19 vs. 6h). Residence times were similar in male and female patients while they were in both genders higher for NOCATE than OCTREO. Consequently, effective dose (ED) for NOCATE (ED 114 and 134 μSv/MBq for man and women, respectively) exceeded that of OCTREO (ED = 61 and 71 μSv/MBq), the latter results being close to the ICRP-published radiation dose of OCTREO (ED = 54 and 71 µSv/MBq, respectively). Differential activity measurement in blood cells and plasma showed that only a minor fraction of NOCATE and OCTREO (<5 % in the mean) was bound to globular blood components. Conclusions: NOCATE showed higher retention in normal organs and delivered roughly twice the radiation dose of OCTREO. The ED of OCTREO in these patients was similar to ICRP80 report when adopting a bladder voiding interval of 2 hours.

Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

AIM: Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. PATIENTS, METHODS: Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. RESULTS: Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. CONCLUSION: 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

Fat oxidation kinetics during exercise in obese individuals

Introduction An impaired ability to oxidize fat may be a factor in the obesity's aetiology (3). Moreover, the exercise intensity (Fatmax) eliciting the maximal fat oxidation rate (MFO) was lower in obese (O) compared with lean (L) individuals (4). However, difference in fat oxidation rate (FOR) during exercise between O and L remains equivocal and little is known about FORs during high intensities (>60% ) in O compared with L. This study aimed to characterize fat oxidation kinetics over a large range of intensities in L and O. Methods 12 healthy L [body mass index (BMI): 22.8±0.4] and 16 healthy O men (BMI: 38.9±1.4) performed submaximal incremental test (Incr) to determine whole-body fat oxidation kinetics using indirect calorimetry. After a 15-min resting period (Rest) and 10-min warm-up at 20% of maximal power output (MPO, determined by a maximal incremental test), the power output was increased by 7.5% MPO every 6-min until respiratory exchange ratio reached 1.0. Venous lactate and glucose and plasma concentration of epinephrine (E), norepinephrine (NE), insulin and non-esterified fatty acid (NEFA) were assessed at each step. A mathematical model (SIN) (1), including three variables (dilatation, symmetry, translation), was used to characterize fat oxidation (normalized by fat-free mass) kinetics and to determine Fatmax and MFO. Results FOR at Rest and MFO were not significantly different between groups (p≥0.1). FORs were similar from 20-60% (p≥0.1) and significantly lower from 65-85% in O than in L (p≤0.04). Fatmax was significantly lower in O than in L (46.5±2.5 vs 56.7±1.9 % respectively; p=0.005). Fat oxidation kinetics was characterized by similar translation (p=0.2), significantly lower dilatation (p=0.001) and tended to a left-shift symmetry in O compared with L (p=0.09). Plasma E, insulin and NEFA were significantly higher in L compared to O (p≤0.04). There were no significant differences in glucose, lactate and plasma NE between groups (p≥0.2). Conclusion The study showed that O presented a lower Fatmax and a lower reliance on fat oxidation at high, but not at moderate, intensities. This may be linked to a: i) higher levels of insulin and lower E concentrations in O, which may induce blunted lipolysis; ii) higher percentage of type II and a lower percentage of type I fibres (5), and iii) decreased mitochondrial content (2), which may reduce FORs at high intensities and Fatmax. These findings may have implications for an appropriate exercise intensity prescription for optimize fat oxidation in O. References 1. Cheneviere et al. Med Sci Sports Exerc. 2009 2. Holloway et al. Am J Clin Nutr. 2009 3. Kelley et al. Am J Physiol. 1999 4. Perez-Martin et al. Diabetes Metab. 2001 5. Tanner et al. Am J Physiol Endocrinol Metab. 2002

Selective tumor localization of radiolabeled anti-human melanoma monoclonal antibody fragment demonstrated in the nude mouse model.

Monoclonal antibodies (Mab) directed against distinct epitopes of the human 240 kD melanoma-associated antigen have been evaluated for their capacity to localize in human melanoma grafted into nude mice. A favorable tumor to normal tissue ratio of 13 was obtained with intact 131I-labeled MAb Me1-14. This ratio was further increased to 43 and 23 by the use of F(ab')2 and Fab fragments, respectively. The specificity of tumor localization was demonstrated by the simultaneous injection of F(ab')2 fragments from MAb Me1-14 and anti-CEA MAb 35, each labeled with a different iodine isotope, into nude mice grafted with a melanoma and colon carcinoma. The fragments from both MAb localized with perfect selectivity in their relevant tumor as shown by differential whole body scanning and by direct measurement of the two isotopes in tumors and normal tissues. These in vivo experimental results suggest that the F(ab')2 fragment from MAb Me1-14 is suitable for melanoma detection by immunoscintigraphy in patients.

The SLC2 family of facilitated hexose and polyol transporters.

The SLC2 family of glucose and polyol transporters comprises 13 members, the glucose transporters (GLUT) 1-12 and the H(+)- myo-inositol cotransporter (HMIT). These proteins all contain 12 transmembrane domains with both the amino and carboxy-terminal ends located on the cytoplasmic side of the plasma membrane and a N-linked oligosaccharide side-chain located either on the first or fifth extracellular loop. Based on sequence comparison, the GLUT isoforms can be grouped into three classes: class I comprises GLUT1-4; class II, GLUT6, 8, 10, and 12 and class III, GLUT5, 7, 9, 11 and HMIT. Despite their sequence similarity and the presence of class-specific signature sequences, these transporters carry various hexoses and HMIT is a H(+)/ myo-inositol co-transporter. Furthermore, the substrate transported by some isoforms has not yet been identified. Tissue- and cell-specific expression of the well-characterized GLUT isoforms underlies their specific role in the control of whole-body glucose homeostasis. Numerous studies with transgenic or knockout mice indeed support an important role for these transporters in the control of glucose utilization, glucose storage and glucose sensing. Much remains to be learned about the transport functions of the recently discovered isoforms (GLUT6-13 and HMIT) and their physiological role in the metabolism of glucose, myo-inositol and perhaps other substrates.

Radioimmunotherapy of human colon carcinoma by 131I-labelled monoclonal anti-CEA antibodies in a nude mouse model.

A mixture of 3 MAbs directed against 3 different CEA epitopes was radiolabelled with 131I and used for the treatment of a human colon carcinoma transplanted s.c. into nude mice. Intact MAbs and F(ab')2 fragments were mixed because it had been shown by autoradiography that these 2 antibody forms can penetrate into different areas of the tumor nodule. Ten days after transplantation of colon tumor T380 a single dose of 600 microCi of 131I MAbs was injected i.v. The tumor grafts were well established (as evidenced by exponential growth in untreated mice) and their size continued to increase up to 6 days after radiolabelled antibody injection. Tumor shrinking was then observed lasting for 4-12 weeks. In a control group injected with 600 microCi of 131I coupled to irrelevant monoclonal IgG, tumor growth was delayed, but no regression was observed. Tumors of mice injected with the corresponding amount of unlabelled antibodies grew like those of untreated mice. Based on measurements of the effective whole-body half-life of injected 131I, the mean radiation dose received by the animals was calculated to be 382 rads for the antibody group and 478 rads for the normal IgG controls. The genetically immunodeficient animals exhibited no increase in mortality, and only limited bone-marrow toxicity was observed. Direct measurement of radioactivity in mice dissected 1, 3 and 7 days after 131I-MAb injection showed that 25, 7.2 and 2.2% of injected dose were recovered per gram of tumor, the mean radiation dose delivered to the tumor being thus more than 5,000 rads. These experiments show that therapeutic doses of radioactivity can be selectively directed to human colon carcinoma by i.v. injection of 131I-labelled anti-CEA MAbs.

(Young Investigator Award) Trabecular Bone Score Helps Classifying Women At Risk Of Fracture Prospectively In The Ofely Study

Introduction: To determine the metabolic effect of teriparatide (TPTD) on bone, 99mTc-MDP skeletal plasma clearance was measured in postmenopausal women with osteoporosis treated with TPTD 20 μg/day. Methods: Ten postmenopausal women with osteoporosis had radionuclide bone scans at baseline, 3, and 18 months after starting TPTD 20 μg/day and after 6 months off therapy. Participants were injected with 600 MBq 99mTc- MDP and whole body bone scans acquired at 10 min, 1, 2, 3, and 4 h. Multiple blood samples were taken between 5 min and 4 h and free 99mTc-MDP measured using ultrafiltration. 99mTc-MDP plasma clearance (Kbone) was evaluated using the Patlak plot method. Regional differences in Kbone were studied by measuring the whole skeleton and subregions. Serum procollagen type I Nterminal propeptide (PINP), bone-specific alkaline phosphatase (BSAP), and urinary N-terminal telopeptide (NTX) were measured at each visit.Discussion: The median increase from baseline in whole skeleton Kbone was 22% (P=0.004) at 3 months and 34% (P= 0.002) at 18 months, decreasing to 0.7% after 6 months off therapy. In subregions, Kbone value increases were statistically significant at 3 months and in all subregions except the pelvis at 18 months. After 6 months off therapy, subregional Kbone values also returned toward baseline. Bone markers increases from baseline were statistically significant at 3 and 18 months (BSAP, 15% and 36%; PINP, 137% and 192%; NTX, 109% and 125%). After 6 months off therapy, PINP and NTX values had declined, though remained above baseline (BSAP, −3%; PINP, 43%; NTX, 56%). Increased Kbone values in the whole body and lower extremities were correlated with increases in most bone markers at 3 and 18 months. Increased skeletal uptake of 99mTc-MDP during treatment with TPTD is indicative of increased bone formation and is supported by increases in bone turnover markers.Conclusion: Changes in Kbone and skeletal uptake measured by radionuclide bone scans in patients taking TPTD are the result of metabolic activity of the drug. These data may provide physicians with useful insights when interpreting bone scan results in this population.

Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice.

Four monoclonal antibodies against carcinoembryonic antigen (CEA) have been selected from 32 hybrids that produce antibodies against this antigen, by the criteria of high affinity for CEA and low cross-reactivity with granulocyte glycoprotein(s). The specificity of tumor localization in vivo of the four MAb, and their F(ab')2 and Fab fragments was compared in nude mice bearing grafts of a serially transplanted, CEA-producing, human colon carcinoma. The distribution of radiolabeled MAb and their fragments after intravenous injection was analyzed by direct measurement of radioactivity in tumor and normal organs, as well as by whole-body scanning and by autoradiography of tumor sections. Paired labeling experiments, in which 131I-labeled antibody or fragments and 125I-labeled control IgG are injected simultaneously, were undertaken to determine the relative tumor uptakes of each labeled protein. The tumor antibody uptake divided by that of control IgG defines the specificity index of localization. Tumor antibody uptakes (as compared with the whole mouse), ranging between 7 and 15, and specificity indices ranging between 3.4 and 6.8, were obtained with the four intact MAb at day 4-5 after injection. With F(ab')2 fragments of the four MAb, at day 3, the tumor antibody uptakes ranged between 12 and 24 and the specificity indices between 5.3 and 8.2. With the Fab fragments prepared from the two most promising MAb, the antibody uptakes reached values of 34 and 82 at day 2-3 and the specificity indices were as high as 12 and 19. The scanning results paralleled those obtained by direct measurement of radioactivity. With intact MAb, tumor grafts of 0.5-1 g gave very contrasted positive scans 3 d after injection. Using MAb fragments, tumors of smaller size were detectable earlier. The best results were obtained with Fab fragments of MAb 35, which gave clear detections of tumors weighing only 0.1 g as early as 48 h after injection. Autoradiographs of tumor sections from mice injected with 125I-labeled MAb demonstrated that the radioactivity was localized in the tumor tissues and not in the stromal connective tissue of mouse origin. The highest radioactivity concentration was localized in areas known to contain CEA such as the pseudolumen of glands and the apical side of carcinoma cells. The penetration of radioactivity in the central part of tumor nodules and the pseudolumen appeared to be increased with the use of MAb fragments.

Fat poetry: a kingdom for PPAR gamma.

Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARgamma agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARgamma in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARgamma modulators.