Muscle fat content is strongly associated with NASH: A longitudinal study in patients with morbid obesity.

BACKGROUND & AIMS: Studies exploring the relationship between muscle fat content and non-alcoholic fatty liver disease (NAFLD) are scarce. Herein, we aimed to evaluate the association of muscle mass and fatty infiltration with biopsy-assessed NAFLD in patients with obesity. METHODS: At inclusion (n = 184) and 12 months after a dietary intervention (n = 15) or bariatric surgery (n = 24), we evaluated NAFLD by liver biopsy, and skeletal muscle mass index (SMI) by CT (CT-SMI) or bioelectrical impedance analysis (BIA-SMI). We developed an index to evaluate absolute fat content in muscle (skeletal muscle fat index [SMFI]) from CT-based psoas muscle density (SMFIPsoas). RESULTS: Muscle mass was higher in patients with NAFLD than in those without (CT-SMI 56.8 ± 9.9 vs. 47.4 ± 6.5 cm2/m2, p <0.0001). There was no association between sarcopenia and non-alcoholic steatohepatitis (NASH). SMFIPsoas was higher in NASH ≥F2 and early NASH F0-1 than in NAFL (78.5 ± 23.6 and 73.1 ± 15.6 vs. 61.2 ± 12.6, p <0.001). A 1-point change in the score for any of the individual cardinal NASH features (i.e. steatosis, inflammation or ballooning) was associated with an increase in SMFIPsoas (all p <0.05). The association between SMFIPsoas and NASH was highly significant even after adjustment for multiple confounders (all p <0.025). After intervention (n = 39), NASH improvement, defined by NAFLD activity score <3 or a 2-point score reduction, was achieved in more than 75% of patients (n = 25 or n = 27, respectively) that had pre-established NASH at inclusion (n = 32) and was associated with a significant decrease in SMFIPsoas (p <0.001). Strikingly, all patients who had ≥11% reduction in SMFIPsoas achieved NASH improvement (14/14, p <0.05). CONCLUSIONS: Muscle fat content, but not muscle mass, is strongly and independently associated with NASH. All individuals who achieved a ≥11% decrease in SMFIPsoas after intervention improved their NASH. These data indicate that muscle fatty infiltration could be a potential marker for (and perhaps a pathophysiological contributor to) NASH. LAY SUMMARY: The fat content in skeletal muscles is highly reflective of the severity of non-alcoholic fatty liver disease (NAFLD) in patients with morbid obesity. In particular, muscle fat content is strongly associated with non-alcoholic steatohepatitis (NASH) and decreases upon NASH improvement. These data indicate that muscle fatty infiltration could be a marker and possible pathophysiological contributor to NASH.

Body fat, cardiovascular risk factors and brain structure in school-age children.

BACKGROUND: In adults, cardiovascular risk factors are known to be associated with brain health. We hypothesized that these associations are already present at school-age. We examined the associations of adverse body fat measures and cardiovascular risk factors with brain structure, including volumetric measures and white matter microstructure, in 10-year-old children. METHODS: We performed a cross-sectional analysis in a population-based prospective cohort study in Rotterdam, the Netherlands. Analyses were based on 3098 children aged 10 years with neuroimaging data and at least one measurement of body fat and cardiovascular risk factors. Body fat measures included body mass index (BMI), fat mass index and android fat mass percentage obtained by Dual-energy X-ray absorptiometry. Cardiovascular risk factors included blood pressure, and serum glucose, insulin and lipids blood concentrations. Structural neuroimaging, including global and regional brain volumes, was quantified by magnetic resonance imaging. DTI was used to assess white matter microstructure, including global fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: As compared to children with a normal weight, those with underweight had a smaller total brain and white matter volumes (differences -18.10 (95% Confidence Interval (CI) -30.97,-5.22) cm3, -10.64 (95% CI -16.82,-4.47) cm3, respectively). In contrast, one SDS (Standard Deviation Score) increase in fat mass index was associated with a smaller gray matter volume (differences -3.48 (95% CI -16.82, -4.47) cm3). Also, one SDS increase in android fat mass percentage was associated with lower white matter diffusivity (difference -0.06 (95% CI -0.10, -0.02) SDS). None of the other cardiovascular risk factors were associated with any of the brain outcomes. CONCLUSIONS: Body fat measures, but not other cardiovascular risk factors, were associated with structural neuroimaging outcomes in school-aged children. Prospective studies are needed to assess causality, direction and long-term consequences of the associations.

Madelung's disease in a non-alcoholic Ethiopian male patient mistaken for obesity: a case report.

BACKGROUND: Madelung's disease (MD) is a rare disorder of fat storage characterized by the presence of diffuse, symmetrical deposition of subcutaneous fat around the neck, shoulder, arm, trunk and thigh. Although its cause is not fully understood, this benign condition is commonly presented among adult males with Mediterranean origin and history of alcohol abuse. Patients often presents with compression of vital structures, cosmetic disfigurement and associated psychosocial problems and systemic comorbidities. It is often under-recognized by physicians, possibly due to obliviousness of the condition and often misdiagnosed as obesity. CASE PRESENTATION: We present a 65-year-old non-alcoholic black Ethiopian man, presented with a slowly growing body fat in his trunk and proximal limbs associated by multiple joint and back pain which got worse recently. He denied any history of chronic alcohol use. On examination, huge, bilateral, non-tender, soft, globular masses in his torso, shoulder, arm and thigh with bilateral breast enlargement. On investigation his biochemical profile was normal except hyperuricemia (10.6 mg/dl). Imaging of the cervical and lumbar vertebrae showed excess subcutaneous fat depositions with degenerative disc disease. Biopsy from the mass revealed non-encapsulated lipoma and he was diagnosed with type II MD. We treated his pain with supportive therapy and discharged in stable condition. The patient deferred surgical treatment. CONCLUSIONS: Madelung's disease is often reported among white adult males with chronic alcoholism. However, our case reported a black man without the typical risk factor which was misdiagnosed as obesity. Hence, clinicians should be aware of MD and need to consider it in their differential diagnosis when encountered with a patient having progressive centripetal fat deposition with or without a history of alcoholism and systemic comorbidities. As early detection of this disorder helps to avoid diagnostic delays and prevent complications through timely interventions which will in turn improves patient quality of life.

Old treatments for new genetic conditions: Sirolimus therapy in a child affected by mosaic overgrowth with fibroadipose hyperplasia.

PIK3CA-related overgrowth spectrum (PROS) are overgrowth diseases involving mesenchymal tissues caused by postzygotic variants in the PIK3CA gene. Fibro-Adipose hyperplasia or Overgrowth (FAO) belongs to PROS. We reported the beneficial effect of oral low-dose sirolimus therapy in a child affected by progressive FAO in term of stabilization of the disease, good tolerability, and easy management.

Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study.

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC- lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects-ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9-5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1-3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3-8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I.1.002-1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002-1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96-0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4-9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24-4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.

Deficits in Col5a2 Expression Result in Novel Skin and Adipose Abnormalities and Predisposition to Aortic Aneurysms and Dissections.

Classic Ehlers-Danlos syndrome (cEDS) is characterized by fragile, hyperextensible skin and hypermobile joints. cEDS can be caused by heterozygosity for missense mutations in genes COL5A2 and COL5A1, which encode the α2(V) and α1(V) chains, respectively, of collagen V, and is most often caused by COL5A1 null alleles. However, COL5A2 null alleles have yet to be associated with cEDS or other human pathologies. We previously showed that mice homozygous null for the α2(V) gene Col5a2 are early embryonic lethal, whereas haploinsufficiency caused aberrancies of adult skin, but not a frank cEDS-like phenotype, as skin hyperextensibility at low strain and dermal cauliflower-contoured collagen fibril aggregates, two cEDS hallmarks, were absent. Herein, we show that ubiquitous postnatal Col5a2 knockdown results in pathognomonic dermal cauliflower-contoured collagen fibril aggregates, but absence of skin hyperextensibility, demonstrating these cEDS hallmarks to arise separately from loss of collagen V roles in control of collagen fibril growth and nucleation events, respectively. Col5a2 knockdown also led to loss of dermal white adipose tissue (WAT) and markedly decreased abdominal WAT that was characterized by miniadipocytes and increased collagen deposition, suggesting α2(V) to be important to WAT development/maintenance. More important, Col5a2 haploinsufficiency markedly increased the incidence and severity of abdominal aortic aneurysms, and caused aortic arch ruptures and dissections, indicating that α2(V) chain deficits may play roles in these pathologies in humans.

Becker Naevus Syndrome of the Lower Body: One Case and Review of the Literature.

Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co-occurrence of a Becker naevus with various cutaneous, muscular and skeletal anomalies. In the majority of cases, abnormalities exclusively consist of ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus reaching from the left buttock to the left calf verified on histological examination. In addition, there was marked hypoplasia of the fatty tissue of the left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of the fatty tissue of the left gluteal area. Underlying muscles and bones were not affected. There was no difference in leg lengths. In addition, we review and discuss the features of Becker naevus syndrome with emphasis on 10 reported cases with involvement of the lower body.

Point-of-Care Ultrasound: Sonographic Posterior Fat Pad Sign: A Case Report and Brief Literature Review.

BACKGROUND: Diagnosis of elbow fracture can sometimes be difficult with plain radiography due to overlapping bones, growth plates, and maturing bones in the pediatric population. The radiographic posterior fat pad (PFP) sign is one of the frequently referenced indirect signs of an occult elbow fracture. This sign can be falsely negative if the sign is subtle, and can be falsely positive when the position of the elbow is not flexed at 90 degrees. CASE REPORT: We discuss a case in which sonographic PFP sign helped to diagnose an elbow fracture. A 57-year-old female presented to the emergency department (ED) after a fall on an outstretched hand. The point-of-care ultrasound (POCUS) was completed identifying an elevated PFP and an anechoic joint fluid collection with innumerous floating hyperechogenic spicules visualized in the olecranon fossa. Diagnosis of a radial head fracture was later confirmed by plain radiograph. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The increase in use and availability of POCUS in the ED makes this a very practical application. Our ability to rapidly perform the ultrasound of the elbow may allow us a more rapid diagnosis of pathology, as well as provide a way to further triage our patients. With time, it may even allow us to avoid routine use of plain radiography.

Myocardial fat overgrowth in Proteus syndrome.

Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Novel application of human morphomics to quantify temporal soft tissues in Pierre Robin and Treacher Collins.

INTRODUCTION: Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls. METHODS: High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized "core" sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant. RESULTS: The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group. CONCLUSIONS: There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.

Coexistence of a pseudolesion and a true lesion in the same location: a rare misleading imaging finding.

Congenital cholesteatoma and asymmetric fatty marrow are both common masses that appear as imaging "lesions" in the petrous apex, but their treatment modalities are very different. Accurate preoperative recognition by computed tomography and magnetic resonance imaging is, therefore, important for planning appropriate management strategies. We report a case with coexisting congenital cholesteatoma and asymmetric fatty marrow in the same petrous bone. The 2 lesions were indistinguishable on high-resolution computed tomographic images and were only identified on fat-suppressed magnetic resonance imaging sequences. This is the first report of these 2 lesions coexisting, leading to a rare misleading imaging finding.

Epiploic appendagitis in a 27-year-old man.

BACKGROUND: Epiploic appendagitis is an ischemic infarction of an epiploic appendage caused by torsion or spontaneous thrombosis of the central draining vein. Epiploic appendagitis is self-limited without surgery, and it is imperative for clinicians to be familiar with this entity. CASE REPORT: A healthy 27-year-old man was admitted due to acute right lower quadrant abdominal pain. Physical examination showed focal abdominal tenderness with slight rebound tenderness. Laboratory tests showed leukocytosis and an increased serum C-reactive protein level. Computed tomography (CT) showed a fatty ovoid pericolonic mass measuring 12 mm in diameter, with a circumferential hyperdense ring that abutted on the ascending colon and was surrounded by ill-defined fat stranding with a hyperdense ring. These findings were diagnostic of primary epiploic appendagitis. The patient was given high-dose antibiotics due to the secondary inflammation involving the parietal peritoneum. CONCLUSIONS: Epiploic appendagitis presents with an abrupt onset of focal abdominal pain and tenderness without significant guarding or rigidity; it is an uncommon and difficult diagnosis. With awareness of this condition, however, evaluation by CT can provide an accurate diagnosis of epiploic appendagitis, distinguishing it from conditions with clinically overlapping manifestations.

Primary epiploic appendagitis: 3 case reports.

Acute Epiploic Appendagitis is a rare self limiting disease that represents ischaemic infarction of an epiploic appendix. It is usually discovered incidentally on imaging of abdomen done for other causes of acute abdominal pain. It is difficult to diagnose clinically due to the lack of pathognomonic clinical features, since it is characterized by a sudden onset of sharp localized pain either in the left or right iliac fossa with minimal gastrointestinal symptoms, which can simulate a surgical clinical picture. Awareness of imaging findings of this entity is important to arrive at a correct diagnosis and to avoid unnecessary hospitalization and surgery. We report cases of three male patients presenting with acute flank pain who were diagnosed as case of Primary epiploic appendagitis. All 3 patients were treated conservatively.

A yellowish subconjunctival lesion in an infant-congenital orbital fat herniation.

A very rare case of a congenital orbital fat herniation is demonstrated. Clinically, the child presented a progressive, small yellowish and mobile mass on the temporal orbital wall of her right eye. Magnetic resonance imaging showed a fat isointensive structure in T1-weighing without contrast enhancement. The possible aetiology of the herniation could be a congenital weakness of the Tenon's capsule or the conjunctival fornix.

Agenesis of the gallbladder with adipose tissue in the gallbladder fossa.

Agenesis of the gallbladder with normal bile ducts is a rare anomaly. More cases have been reported preoperatively because of the increased awareness of this entity. However some cases remain difficult to diagnosis. We report such a case. A symptomatic male patient (age 45) was diagnosed with chronic atrophic cholecystitis and cholecystlithiasis by ultrasonography and computed tomography scan. The images revealed solid tissue in the gallbladder fossa. However, during laparoscopic exploration no gallbladder or ectopic gallbladder was found. Only adipose tissue and the gallbladder artery were identified during the operation. Gallbladder agenesis was diagnosed postoperatively. It still remains a challenge to determine surgical intervention in these cases.

Child Body Fat and Body Mass Index: Which Determinants are Most Important?

The purpose of this study was to examine child and parent determinants of children's body fat percentage (BF%) along with their body mass index percentile (BMIp). Children's BF% and BMIp auger lifelong health risks when elevated, and one in five children are affected. Participants (N = 135) included 62% female children; 50.7% Caucasian, 31.7% Hispanic, and 8.5% African American. Children were aged 9-15 years (2% underweight, 47.9% normal weight, 19.7% overweight, and 24.6% obese). Parent BMI average was 30.67 (1.4% underweight, 20.4% normal weight, 23.9% overweight, 40% obese, and 7% extreme obesity); 77.5% of the participating parents were mothers. Following multiple imputations, path analyses were conducted of child and parent determinants of children's BF% and BMIp. Children's BF% and BMIp were related to parents' concern about overweight and children's perception of that concern. For children of overweight or obese parents, who are at highest risk for obesity, assessing the parents' concern is the highest priority.

Clinical outcome after lipectomy in the management of patients with human immunodeficiency virus-associated dorsocervical fat accumulation: An observational cohort study.

Lipo-accumulation of the dorsocervical fat pad ("buffalo hump") is a complication observed in people living with human immunodeficiency virus (HIV). We described the clinical outcome of people living with HIV with "buffalo hump" treated by excisional lipectomy.From April 2013 to March 2018, medical records of people living with HIV, who received care in our hospital have been evaluated. Among them, patients with dorsocervical fat accumulation treated by excisional lipectomy have been retrospectively assessed.Nine patients with "buffalo hump" among 2886 people living with HIV (3.1‰, 9/2886) were included. Eight were women with a mean age of 47.9 ±â€Š8.0 years old (range, 36-60). Most of them have been infected by blood transfusion (77%, 7/9) and the mean duration of HIV infection was 14.1 ±â€Š5.5 years (range, 6-22). The mean duration for antiretroviral therapy was 8.8 ±â€Š2.1 years (range, 6-11). The mean pre-ART CD4+ T cell count was 91.3 ±â€Š76.5 cells/µL (range, 4-233) and 477.4 ±â€Š271.8 cells/µL (range, 114-926) at the time of surgery. All 9 patients underwent excisional lipectomy of their hypertrophied dorsocervical fat pad. The mean size of the excised specimens was 14 × 11 × 6 cm. The median follow-up time was 24 months (range, 2-60), all 9 patients reported satisfaction with their results, with no recurrence has been observed.Corrective surgery used to treat localized fat accumulations in people living with HIV with "buffalo hump" showed a favorable effect and can therefore be considered when necessary. Whereas drugs such as integrase inhibitors may avoid lipo-accumulation related syndrome and should be given to people living with HIV in China.

Phacomatosis cesioflammea with unilateral lipohypoplasia.

Phacomatosis cesioflammea is characterized by the co-existence of a large nevus cesius (i.e., aberrant Mongolian spot, or nevus fuscocoeruleus) and an extensive nevus flammeus (i.e., port-wine stain). This sporadic genetic skin disorder represents a particular type of phacomatosis pigmentovascularis, a group of disorders that may reflect twin spotting. We report on a 28-year-old woman with aberrant Mongolian spots, bilateral melanosis bulbi, and systematized nevus flammeus partly intermingled with nevus anemicus. Moreover, pronounced lipohypoplasia of the right buttock and thigh as well as hypoplasia of the right breast are present. This anomaly of fatty tissue has not previously been reported in phacomatosis cesioflammea and further expands the clinical spectrum of this mosaic disorder. The patchy distribution of lipohypoplasia and its spatial relationship with vascular lesions strongly support the hypothesis of a postzygotic recombination event.

Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion.

Langer-Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1 and the adjacent TRPS1 gene. We report on a boy with an oligo array-cgh characterized small microdeletion involving EXT1 alone but with some features of Langer-Giedion syndrome suggesting a functional disturbance of TRPS1. This boy, in addition to a mild Langer-Giedion like phenotype, also had some unusual features including prominent toe pads and fat pads on the soles of his feet similar to those described in Pierpont syndrome.

Dysregulation of the peroxisome proliferator-activated receptor target genes by XPD mutations.

Mutations in the XPD subunit of TFIIH give rise to human genetic disorders initially defined as DNA repair syndromes. Nevertheless, xeroderma pigmentosum (XP) group D (XP-D) patients develop clinical features such as hypoplasia of the adipose tissue, implying a putative transcriptional defect. Knowing that peroxisome proliferator-activated receptors (PPARs) are implicated in lipid metabolism, we investigated the expression of PPAR target genes in the adipose tissues and the livers of XPD-deficient mice and found that (i) some genes are abnormally overexpressed in a ligand-independent manner which parallels an increase in the recruitment of RNA polymerase (pol) II but not PPARs on their promoter and (ii) upon treatment with PPAR ligands, other genes are much less induced compared to the wild type, which is due to a lower recruitment of both PPARs and RNA pol II. The defect in transactivation by PPARs is likely attributable to their weaker phosphorylation by the cdk7 kinase of TFIIH. Having identified the phosphorylated residues in PPAR isotypes, we demonstrate how their transactivation defect in XPD-deficient cells can be circumvented by overexpression of either a wild-type XPD or a constitutively phosphorylated PPAR S/E. This work emphasizes that underphosphorylation of PPARs affects their transactivation and consequently the expression of PPAR target genes, thus contributing in part to the XP-D phenotype.