Cellulitis in the Emergency Department: A prospective cohort study with patient-centred follow-up.

OBJECTIVE: There is substantial practice variation in the management of cellulitis with limited prospective studies describing the course of cellulitis after diagnosis. We aimed to describe the demographics, clinical features (erythema, warmth, swelling and pain), patient-reported disease trajectory and medium-term follow-up for ED patients with cellulitis. METHODS: Prospective observational cohort study of adults diagnosed with cellulitis in two EDs in Southeast Queensland, Australia. Patients with (peri)orbital cellulitis and abscess were excluded. Data were obtained from a baseline questionnaire, electronic medical records and follow-up questionnaires at 3, 7 and 14 days. Clinician adjudication of day 14 cellulitis cure was compared to patient assessment. Descriptive analyses were conducted. RESULTS: Three-hundred patients (mean age 50 years, SD 19.9) with cellulitis were enrolled, predominantly affecting the lower limb (75%). Cellulitis features showed greatest improvement between enrolment and day 3. Clinical improvement continued gradually at days 7 and 14 with persistent skin erythema (41%) and swelling (37%) at day 14. Skin warmth was the feature most likely to be resolved at each time point. There was a discrepancy in clinician and patient assessment of cellulitis cure at day 14 (85.8% vs. 52.8% cured). CONCLUSIONS: A clinical response of cellulitis features can be expected at day 3 with ongoing slower improvement over time. Over one third of patients had erythema or swelling at day 14. Patients are less likely than clinicians to deem their cellulitis cured at day 14. Future research should include parallel patient and clinician evaluation of cellulitis to help develop clearer definitions of treatment failure and cure.

Liraglutide modulates adhesion molecules and enhances cell properties in three-dimensional cultures of olfactory ensheathing cells.

Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method. Three-dimensional (3D) cell culture systems potentially offer a powerful approach for cell production and delivery options. To further optimise the use of OECs, strategies to promote cell viability and maintain cell behaviours in 3D cultures become important. We previously demonstrated an anti-diabetic drug, liraglutide, could modulate OEC migration and re-model extracellular matrix in two-dimensional (2D) cultures. In the present study, we further investigated its beneficial effects in our 3D culture system using primary OECs. OECs treated with liraglutide at 100 nM showed improved cell viability and had modulated expression of N-cadherin and ß1-integrin (two important cell adhesion molecules). When formed into 3D spheroids, the pre-treated OECs generated spheroids with an increased volume and a decreased cell density compared to control spheroids. OECs that subsequently migrated out of the liraglutide pre-treated spheroids had higher capacity for migration with increased duration and length, which was attributed to a reduction in the pauses during the migration. Moreover, OECs that migrated out from liraglutide spheroids had a more bipolar morphology consistent with higher migratory capacity. In summary, liraglutide improved the viability of OECs, modulated cell adhesion molecules, and resulted in stable 3D cell constructs which conferred enhanced migratory capacity on the OECs. Overall, liraglutide may potentially improve the therapeutic use of OECs for neural repair by enhancing the generation of stable 3D constructs and increasing the migratory behaviour of OECs.

Specializations in optic flow encoding in the pretectum of hummingbirds and zebra finches.

All visual animals experience optic flow-global visual motion across the retina, which is used to control posture and movement.1 The midbrain circuitry for optic flow is highly conserved in vertebrates,2-6 and these neurons show similar response properties across tetrapods.4,7-16 These neurons have large receptive fields and exhibit both direction and velocity selectivity in response to large moving stimuli. Hummingbirds deviate from the typical vertebrate pattern in several respects.17,18 Their lentiformis mesencephali (LM) lacks the directional bias seen in other tetrapods and has an overall bias for faster velocities. This led Ibbotson19 to suggest that the hummingbird LM may be specialized for hovering close to visual structures, such as plants. In such an environment, even slight body motions will translate into high-velocity optic flow. A prediction from this hypothesis is that hummingbird LM neurons should be more responsive to large visual features. We tested this hypothesis by measuring neural responses of hummingbirds and zebra finches to sine wave gratings of varying spatial and temporal frequencies. As predicted, the hummingbird LM displayed an overall preference for fast optic flow because neurons were biased to lower spatial frequencies. These neurons were also tightly tuned in the spatiotemporal domain. We found that the zebra finch LM specializes along another domain: many neurons were initially tuned to high temporal frequencies followed by a shift in location and orientation to slower velocity tuning. Collectively, these results demonstrate that the LM has distinct and specialized tuning properties in at least two bird species.

Selection of Image Texture Analysis and Color Model in the Advanced Image Processing of Thermal Images of Horses following Exercise.

As the detection of horse state after exercise is constantly developing, a link between blood biomarkers and infrared thermography (IRT) was investigated using advanced image texture analysis. The aim of the study was to determine which combinations of RGB (red-green-blue), YUI (brightness-UV-components), YIQ (brightness-IQ-components), and HSB (hue-saturation-brightness) color models, components, and texture features are related to the blood biomarkers of exercise effect. Twelve Polish warmblood horses underwent standardized exercise tests for six consecutive days. Both thermal images and blood samples were collected before and after each test. All 144 obtained IRT images were analyzed independently for 12 color components in four color models using eight texture-feature approaches, including 88 features. The similarity between blood biomarker levels and texture features was determined using linear regression models. In the horses' thoracolumbar region, 12 texture features (nine in RGB, one in YIQ, and two in HSB) were related to blood biomarkers. Variance, sum of squares, and sum of variance in the RGB were highly repeatable between image processing protocols. The combination of two approaches of image texture (histogram statistics and gray-level co-occurrence matrix) and two color models (RGB, YIQ), should be considered in the application of digital image processing of equine IRT.

The Effect of Rider:Horse Bodyweight Ratio on the Superficial Body Temperature of Horse's Thoracolumbar Region Evaluated by Advanced Thermal Image Processing.

Appropriate matching of rider-horse sizes is becoming an increasingly important issue of riding horses' care, as the human population becomes heavier. Recently, infrared thermography (IRT) was considered to be effective in differing the effect of 10.6% and 21.3% of the rider:horse bodyweight ratio, but not 10.1% and 15.3%. As IRT images contain many pixels reflecting the complexity of the body's surface, the pixel relations were assessed by image texture analysis using histogram statistics (HS), gray-level run-length matrix (GLRLM), and gray level co-occurrence matrix (GLCM) approaches. The study aimed to determine differences in texture features of thermal images under the impact of 10-12%, >12 ≤15%, >15 <18% rider:horse bodyweight ratios, respectively. Twelve horses were ridden by each of six riders assigned to light (L), moderate (M), and heavy (H) groups. Thermal images were taken pre- and post-standard exercise and underwent conventional and texture analysis. Texture analysis required image decomposition into red, green, and blue components. Among 372 returned features, 95 HS features, 48 GLRLM features, and 96 GLCH features differed dependent on exercise; whereas 29 HS features, 16 GLRLM features, and 30 GLCH features differed dependent on bodyweight ratio. Contrary to conventional thermal features, the texture heterogeneity measures, InvDefMom, SumEntrp, Entropy, DifVarnc, and DifEntrp, expressed consistent measurable differences when the red component was considered.

Response properties of optic flow neurons in the accessory optic system of hummingbirds versus zebra finches and pigeons.

Optokinetic responses function to maintain retinal image stabilization by minimizing optic flow that occurs during self-motion. The hovering ability of hummingbirds is an extreme example of this behavior. Optokinetic responses are mediated by direction-selective neurons with large receptive fields in the accessory optic system (AOS) and pretectum. Recent studies in hummingbirds showed that, compared with other bird species, 1) the pretectal nucleus lentiformis mesencephali (LM) is hypertrophied, 2) LM has a unique distribution of direction preferences, and 3) LM neurons are more tightly tuned to stimulus velocity. In this study, we sought to determine if there are concomitant changes in the nucleus of the basal optic root (nBOR) of the AOS. We recorded the visual response properties of nBOR neurons to large-field-drifting random dot patterns and sine-wave gratings in Anna's hummingbirds and zebra finches and compared these with archival data from pigeons. We found no differences with respect to the distribution of direction preferences: Neurons responsive to upward, downward, and nasal-to-temporal motion were equally represented in all three species, and neurons responsive to temporal-to-nasal motion were rare or absent (<5%). Compared with zebra finches and pigeons, however, hummingbird nBOR neurons were more tightly tuned to stimulus velocity of random dot stimuli. Moreover, in response to drifting gratings, hummingbird nBOR neurons are more tightly tuned in the spatiotemporal domain. These results, in combination with specialization in LM, support a hypothesis that hummingbirds have evolved to be "optic flow specialists" to cope with the optomotor demands of sustained hovering flight.NEW & NOTEWORTHY Hummingbirds have specialized response properties to optic flow in the pretectal nucleus lentiformis mesencephali (LM). The LM works with the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) to process global visual motion, but whether the neural response specializations observed in the LM extend to the nBOR is unknown. Hummingbird nBOR neurons are more tightly tuned to visual stimulus velocity, and in the spatiotemporal domain, compared with two nonhovering species.

Liraglutide modulates olfactory ensheathing cell migration with activation of ERK and alteration of the extracellular matrix.

Transplantation of olfactory ensheathing cells (OECs) is a promising approach for repairing the injured nervous system that has been extensively trialed for nervous system repair. However, the method still needs improvement and optimization. One avenue of improving outcomes is to stimulate OEC migration into the injury site. Liraglutide is a glucagon-like peptide-1 receptor agonist used for management of diabetes and obesity. It has been shown to be neuroprotective and to promote cell migration, but whether it can stimulate glial cells remains unknown. In the current study, we investigated the effects of liraglutide on OEC migration and explored the involved mechanisms. We showed that liraglutide at low concentration (100 nM) overall promoted OEC migration over time. Liraglutide modulated the migratory behavior of OECs by reducing time in arrest, and promoted random rather than straight migration. Liraglutide also induced a morphological change of primary OECs towards a bipolar shape consistent with improved migration. We found that liraglutide activated extracellular signal-regulated kinase (ERK), which has key roles in cell migration; the timing of ERK activation correlated with stimulation of migration. Furthermore, liraglutide also modulated the extracellular matrix by upregulating laminin-1 and down-regulating collagen IV. In summary, we found that liraglutide can stimulate OEC migration and re-model the extracellular matrix to better promote cell migration, and possibly also to become more conducive for axonal regeneration. Thus, liraglutide may improve OEC transplantation outcomes.

Advances in Thermal Image Analysis for the Detection of Pregnancy in Horses Using Infrared Thermography.

Infrared thermography (IRT) was applied as a potentially useful tool in the detection of pregnancy in equids, especially native or wildlife. IRT measures heat emission from the body surface, which increases with the progression of pregnancy as blood flow and metabolic activity in the uterine and fetal tissues increase. Conventional IRT imaging is promising; however, with specific limitations considered, this study aimed to develop novel digital processing methods for thermal images of pregnant mares to detect pregnancy earlier with higher accuracy. In the current study, 40 mares were divided into non-pregnant and pregnant groups and imaged using IRT. Thermal images were transformed into four color models (RGB, YUV, YIQ, HSB) and 10 color components were separated. From each color component, features of image texture were obtained using Histogram Statistics and Grey-Level Run-Length Matrix algorithms. The most informative color/feature combinations were selected for further investigation, and the accuracy of pregnancy detection was calculated. The image texture features in the RGB and YIQ color models reflecting increased heterogeneity of image texture seem to be applicable as potential indicators of pregnancy. Their application in IRT-based pregnancy detection in mares allows for earlier recognition of pregnant mares with higher accuracy than the conventional IRT imaging technique.

Induction of Complete Transection-Type Spinal Cord Injury in Mice.

Spinal cord injury (SCI) largely leads to irreversible and permanent loss of function, most commonly as a result of trauma. Several treatment options, such as cell transplantation methods, are being researched to overcome the debilitating disabilities arising from SCI. Most pre-clinical animal trials are conducted in rodent models of SCI. While rat models of SCI have been widely used, mouse models have received less attention, even though mouse models can have significant advantages over rat models. The small size of mice equates to lower animal maintenance costs than for rats, and the availability of numerous transgenic mouse models is advantageous for many types of studies. Inducing repeatable and precise injury in the animals is the primary challenge for SCI research, which in small rodents requires high-precision surgery. The transection-type injury model has been a commonly used injury model over the last decade for transplantation-based therapeutic research, however a standardized method for inducing a complete transection-type injury in mice does not exist. We have developed a surgical protocol for inducing a complete transection type injury in C57BL/6 mice at thoracic vertebral level 10 (T10). The procedure uses a small tip drill instead of rongeurs to precisely remove the lamina, after which a thin blade with rounded cutting edge is used to induce the spinal cord transection. This method leads to reproducible transection-type injury in small rodents with minimal collateral muscle and bone damage and therefore minimizes confounding factors, specifically where behavioral functional outcomes are analyzed.

Direct puncture of the V3 segment of the vertebral artery in acute basilar artery stroke: an alternative approach in desperate circumstances.

A patient in his mid-40s presented with acute basilar artery thrombosis 7 hours postsymptom onset. Initial attempts to perform mechanical thrombectomy (MT) via the femoral and radial arterial approaches were unsuccessful as the left vertebral artery (VA) was occluded at its origin and the right VA terminated in the posterior inferior cerebellar artery territory, without contribution to the basilar system. MT was thus performed following ultrasound-guided direct arterial puncture of the left VA in its V3 segment, with antegrade advancement of a 4 French radial access sheath. First pass thrombolyisis in cerebral infarction (TICI) 3 recanalisation achieved with a 6 mm Solitaire stent retriever and concurrent aspiration on the 4 French sheath. Vertebral closure achieved with manual compression.

Outcomes after Thrombectomy in Belfast: Mothership and Drip-and-Ship in the Real World.

BACKGROUND: Mechanical thrombectomy has revolutionised the treatment of acute ischaemic stroke due to large vessel occlusion. It is well recognised that patients are more likely to benefit when reperfusion happens quickly, however, there is uncertainty as to how best to deliver this service. OBJECTIVES: To compare outcomes of patients in Northern -Ireland who underwent thrombectomy via direct admission to the single endovascular centre (mothership [MS]) with those transferred from primary stroke centres (drip-and-ship [DS]). METHODS: Analysis was conducted on the records of all patients who underwent thrombectomy from January 2014 to December 2017 inclusive. The primary outcome measure was 3 months functional independence (modified Rankin Score [mRS] 0-2). Secondary outcome measures were full recovery (mRS 0) at 3 months, symptomatic intracranial haemorrhage (sICH) rates and mortality rates. RESULTS: Two hundred fourteen patients underwent thrombectomy (MS 124, DS 90). Patients in the MS group were older (median 73 vs. 70 years, p = 0.026), but there was no significant difference in baseline National Institutes of Health Stroke Scale (median 15 MS vs. 16.5 DS, p = 0.162) or thrombolysis rates (41.9% MS vs. 54.4% DS, p = 0.070) between the groups. Time from stroke onset to arrival at thrombectomy centre was shorter in the MS group (median 71 vs. 218 min, p < 0.001) but door to groin puncture time was shorter in the DS group (median 30 vs. 60 min, p < 0.001). There was no significant difference in 3 months functional independence (51.6% MS vs. 62.2% DS, p = 0.123), or in the secondary outcome measures of full recovery (21.8% MS vs. 12.2% DS, p = 0.071), sICH (MS 0.8%, DS 4.4%, p = 0.082) and mortality (MS 24.2%, DS 20.0%, p = 0.468). CONCLUSIONS: Our analysis showed similar outcomes after thrombectomy in the MS and DS groups. For patients potentially eligible for thrombectomy, rapid access to the endovascular centre is essential to optimise both the number of patients treated and the outcomes achieved.

ESCAPE to Reality, Post-Trial Outcomes in an ESCAPE Centre: A Retrospective Case-Control Study.

INTRODUCTION: The Royal Victoria Hospital, Belfast provides the regional neuroendovascular service for Northern Ireland and was an enrolling centre for the ESCAPE endovascular stroke trial. Our aim was to assess outcomes for patients presenting with acute stroke following discontinuation of trial enrolment at our centre. METHODS: We collected data on all patients presenting with acute stoke between Nov-1st-2014 and Oct-31st-2015 who received endovascular treatment or received IV thrombolysis (IV-tPA) alone. ESCAPE eligibility of each patient was assessed. Primary outcome was modified Rankin Score (mRS) at 3 months. RESULTS: 129 patients presented with acute stoke symptoms during the time period; 56/129 (43.4%) patients in the intervention group and 73/129 (56.5%) patients in the control group. In the interventional group, 42/56 (75%) were considered ESCAPE eligible and 14/56 (25%) were considered ESCAPE ineligible. 30/42 (71.4%) ESCAPE eligible patients had a positive functional outcome at 3 months compared to 9/14 (64.2%) ESCAPE ineligible patients. In the control group, 37 (50.7%) had identifiable thrombotic occlusion and 13/37 (35.1%) were considered eligible for intervention. 4/13 (30.8%) achieved functional independence (mRS<3) at 3 months.There was a statistically significant difference in functional independence in those who underwent endovascular therapy compared to the control group (p= 0.04). CONCLUSION: ESCAPE eligible patients in our centre had favourable outcome rates superior to the published trial data. ESCAPE ineligible patients tended to do slightly less well, but still better than the favourable outcome rates achieved with IVtPA alone. There is potentially a wide discordance between the threshold for futility and trial eligibility criteria when considering endovascular treatment for acute ischaemic stroke.

Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.

INTRODUCTION: Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. METHODS: Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. RESULTS: Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. CONCLUSIONS: In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.

Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis.

Insulin and insulin-like growth factor 1 (IGF-1) are major regulators of muscle protein and glucose homeostasis. To determine how these pathways interact, we generated mice with muscle-specific knockout of IGF-1 receptor (IGF1R) and insulin receptor (IR). These MIGIRKO mice showed >60% decrease in muscle mass. Despite a complete lack of insulin/IGF-1 signaling in muscle, MIGIRKO mice displayed normal glucose and insulin tolerance. Indeed, MIGIRKO mice showed fasting hypoglycemia and increased basal glucose uptake. This was secondary to decreased TBC1D1 resulting in increased Glut4 and Glut1 membrane localization. Interestingly, overexpression of a dominant-negative IGF1R in muscle induced glucose intolerance in MIGIRKO animals. Thus, loss of insulin/IGF-1 signaling impairs muscle growth, but not whole-body glucose tolerance due to increased membrane localization of glucose transporters. Nonetheless, presence of a dominant-negative receptor, even in the absence of functional IR/IGF1R, induces glucose intolerance, indicating that interactions between these receptors and other proteins in muscle can impair glucose homeostasis.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.

Interplay between FGF21 and insulin action in the liver regulates metabolism.

The hormone FGF21 regulates carbohydrate and lipid homeostasis as well as body weight, and increasing FGF21 improves metabolic abnormalities associated with obesity and diabetes. FGF21 is thought to act on its target tissues, including liver and adipose tissue, to improve insulin sensitivity and reduce adiposity. Here, we used mice with selective hepatic inactivation of the IR (LIRKO) to determine whether insulin sensitization in liver mediates FGF21 metabolic actions. Remarkably, hyperglycemia was completely normalized following FGF21 treatment in LIRKO mice, even though FGF21 did not reduce gluconeogenesis in these animals. Improvements in blood sugar were due in part to increased glucose uptake in brown fat, browning of white fat, and overall increased energy expenditure. These effects were preserved even after removal of the main interscapular brown fat pad. In contrast to its retained effects on reducing glucose levels, the effects of FGF21 on reducing circulating cholesterol and hepatic triglycerides and regulating the expression of key genes involved in cholesterol and lipid metabolism in liver were disrupted in LIRKO mice. Thus, FGF21 corrects hyperglycemia in diabetic mice independently of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism.

Lessons on conditional gene targeting in mouse adipose tissue.

Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ~2% of spermatozoa. Thus, different "adipocyte-specific" Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.

Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance.

Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity.