Hydroxysteroid 17ß-dehydrogenase 11 accumulation on lipid droplets promotes ethanol-induced cellular steatosis.

Lipid droplets (LDs) are fat-storing organelles enclosed by a phospholipid monolayer, which harbors membrane-associated proteins that regulate distinct LD functions. LD proteins are degraded by the ubiquitin-proteasome system (UPS) and/or by lysosomes. Because chronic ethanol (EtOH) consumption diminishes the hepatic functions of the UPS and lysosomes, we hypothesized that continuous EtOH consumption slows the breakdown of lipogenic LD proteins targeted for degradation, thereby causing LD accumulation. Here, we report that LDs from livers of EtOH-fed rats exhibited higher levels of polyubiquitylated-proteins, linked at either lysine 48 (directed to proteasome) or lysine 63 (directed to lysosomes) than LDs from pair-fed control rats. MS proteomics of LD proteins, immunoprecipitated with UB remnant motif antibody (K-ε-GG), identified 75 potential UB proteins, of which 20 were altered by chronic EtOH administration. Among these, hydroxysteroid 17ß-dehydrogenase 11 (HSD17ß11) was prominent. Immunoblot analyses of LD fractions revealed that EtOH administration enriched HSD17ß11 localization to LDs. When we overexpressed HSD17ß11 in EtOH-metabolizing VA-13 cells, the steroid dehydrogenase 11 became principally localized to LDs, resulting in elevated cellular triglycerides (TGs). Ethanol exposure augmented cellular TG, while HSD17ß11 siRNA decreased both control and EtOH-induced TG accumulation. Remarkably, HSD17ß11 overexpression lowered the LD localization of adipose triglyceride lipase. EtOH exposure further reduced this localization. Reactivation of proteasome activity in VA-13 cells blocked the EtOH-induced rises in both HSD17ß11 and TGs. Our findings indicate that EtOH exposure blocks HSD17ß11 degradation by inhibiting the UPS, thereby stabilizing HSD17ß11 on LD membranes, to prevent lipolysis by adipose triglyceride lipase and promote cellular LD accumulation.

Program development and implementation outcomes of a statewide addiction consultation service: Maryland Addiction Consultation Service (MACS).

Background: As the opioid epidemic continues, there is a mounting sense of urgency to improve access to high-quality early identification and treatment services. However, the need is outpacing capacity in many states and effective solutions to support primary care and specialty prescribers to identify and treat more patients with opioid use disorders are still emerging. This paper describes one state's approach to increase access to medication for opioid use disorders (MOUD) through development and implementation of a statewide addiction consultation service: Maryland Addiction Consultation Service (MACS). Methods: Program components include a warmline, outreach and training, and resource and referral linkages for prescribers based on related consultation service models and documented barriers to prescribing MOUDs. Results: Initial implementation outcomes indicate service components are being adopted as intended and by the target audience; many prescribers who engaged with the service have their buprenorphine waiver (44%) but do not have any additional formal addiction training (57%). Also, statewide penetration is promising with prescriber engagement in 100% of counites, however only 33% of counties in engaged in all four types of MACS services. Most calls (61%) originated from urban counties. Conclusions: The MACS program increases access to specialty addiction medicine consultation and training through use of technology. MACS can serve as a model for other states looking to bridge the gap in access to addiction treatment.

Pediatric Primary Care Provider Comfort with Mental Health Practices: A Needs Assessment of Regions with Shortages of Treatment Access.

OBJECTIVES: Nearly 50% of children with a mental health concern do not receive treatment. Child Psychiatry Access Programs like Behavioral Health Integration in Pediatric Primary Care (BHIPP) address regional shortages of mental health treatment access by providing training and consultation to primary care providers (PCPs) in managing mental health concerns. This study assessed PCPs' comfort with mental health practices to inform expansion of BHIPP services. METHODS: Pediatric PCPs in 114 practices in three rural regions of Maryland were recruited to participate in a survey about their comfort with mental health practices and access to mental health providers for referral. Descriptives, Friedman's test, and post hoc pairwise comparisons were used to examine survey responses. RESULTS: Participants were 107 PCPs. Most respondents were physicians (53.3%) or nurse practitioners/physician's assistants (39.3%). Friedman's test, χ2(7)= 210.15, p<.001, revealed significant within and between-group differences in PCP comfort with mental health practices. Post hoc pairwise comparisons indicated greater comfort providing mental health screening and referrals compared to prescribing psychiatric medications, providing psychoeducation or in-office mental health interventions. A Wilcoxon-signed rank test showed significantly more respondents agreed they could find a therapist than a psychiatrist in a timely manner, Z= -5.93, p<.001. CONCLUSIONS: Pediatric PCPs were more comfortable with providing mental health assessment and referrals than treatment. However, PCPs reported difficulty finding therapists and psychiatrists for their patients. Findings underscore the need for longitudinal training to increase PCP comfort with mental health treatment. Additionally, strategies such as telepsychiatry are needed to address the disproportionate need for child psychiatrists.

Grape Cells (Multinucleated Keratinocytes) in Noninfectious Dermatoses: Case Series and Review of the Literature.

Multinucleated keratinocytes (also known as multinucleated epidermal giant cells) are a frequently overlooked histological finding in noninfectious inflammatory dermatoses. They are sometimes found in conditions characterized by chronic rubbing and pruritus, such as lichen simplex chronicus or prurigo nodularis, and may be a helpful clue in making the clinical diagnosis. This finding must be differentiated from other conditions characterized by multinucleated keratinocytes on histopathology, specifically herpes simplex, varicella zoster, or measles viral infections. The authors present a case series of 2 patients with unique clinical noninfectious diagnoses but similar histopathologic findings on biopsy. The histopathologic findings on both cases demonstrated multinucleated keratinocytes, which were related to manipulation of the epidermis.

Metrics for assessing improvements in primary health care.

Metrics focus attention on what is important. Balanced metrics of primary health care inform purpose and aspiration as well as performance. Purpose in primary health care is about improving the health of people and populations in their community contexts. It is informed by metrics that include long-term, meaning- and relationship-focused perspectives. Aspirational uses of metrics inspire evolving insights and iterative improvement, using a collaborative, developmental perspective. Performance metrics assess the complex interactions among primary care tenets of accessibility, a whole-person focus, integration and coordination of care, and ongoing relationships with individuals, families, and communities; primary health care principles of inclusion and equity, a focus on people's needs, multilevel integration of health, collaborative policy dialogue, and stakeholder participation; basic and goal-directed health care, prioritization, development, and multilevel health outcomes. Environments that support reflection, development, and collaborative action are necessary for metrics to advance health and minimize unintended consequences.

Graft-versus-host disease-associated angiomatosis: a clinicopathologically distinct entity.

BACKGROUND: Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifestations. Isolated case reports describe eruptive angiomas in this setting. OBJECTIVE: We sought to provide a clinical and pathologic description of vascular proliferations in patients with GVHD. METHODS: Cases of documented GVHD associated with vascular proliferations were collected from the National Institutes of Health, Ohio State University, and MD Anderson Cancer Center. RESULTS: Eleven patients with a diagnosis of GVHD who developed vascular proliferations were identified. All patients manifested sclerotic type chronic GVHD of the skin. Vascular lesions were first documented a median of 44 months after transplantation and occurred primarily on the lower extremities or trunk. Histopathology revealed anastomosing networks of thin-walled vascular proliferations in a vague lobular growth pattern, with overlying epidermal acanthosis, peripheral collarette, ulceration, and disorganized fibroblast-rich and fibrotic stroma. Improvement was noted in 1 patient treated with propranolol and sirolimus and 1 patient with electrocautery. LIMITATIONS: Given the retrospective nature of the study, the overall incidence of vascular lesions in patients with GVHD is unknown. Histopathology was present for review on only 3 of 11 patients. CONCLUSION: The phenomenon of vascular lesions appears to be relatively specific for sclerotic type chronic GVHD when compared with other fibrosing diseases. We propose the term "graft-versus-host disease-associated angiomatosis" to describe this entity.

A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster.

Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP-Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications.

Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans.

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

Increased risks of Maternal Mental Health Conditions Following the COVID-19 Pandemic.

Background: Women are at an increased risk of developing psychiatric conditions such as anxiety and depression during pregnancy. Psychiatric conditions during pregnancy can put mothers and fetuses at risk of worse physical and mental health before, during, and after the completion of a pregnancy. Previous research indicates that women pregnant during COVID-19 were at a greater risk of developing mental health conditions and being exposed to stressors. While most of the research in the field focuses solely on maternal mental health or interactions between stressors and maternal mental health, little research has been done comparing maternal mental health, demographic variables, and socioeconomic variables across pre-, during-, and post-COVID-19 time periods. Methods: We conducted an observational cohort study of 703 mothers divided into pre-, during-, and post-COVID-19 groups based on time of enrollment. Results: Rates of maternal anxiety (p < 0.001), medication use for anxiety (p < 0.001), depression (p < 0.001), medication use for depression (p < 0.001), history of postpartum depression (p < 0.001), and medication use for other psychiatric conditions (p < 0.001) significantly increased during COVID-19 and remained at elevated levels post-COVID-19 compared with pre-COVID-19. Income >150% of the poverty level (p = 0.003), food security level (p = 0.010), marital status (p = 0.001), and private insurance type (p < 0.001) were significantly increased during COVID-19 compared with pre-COVID-19 levels. Conclusions: Future work should focus on stratifying the effects of the COVID-19 pandemic on maternal mental health by race and ethnicity and establishing guidelines to support maternal mental health during epidemics and pandemics.

Perforating granulomatous dermatitis reaction to exogenous tattoo pigment: a case report and review of the literature.

: The majority of cutaneous hypersensitivity reactions to exogenous tattoo pigments can be histologically classified as lichenoid or granulomatous. The etiology is still uncertain but is generally accepted to be a delayed-type hypersensitivity reaction to either the pigment itself or its carrier solution. In this report, we review the literature concerning adverse reactions to tattoos. In addition, we describe the second case of a localized granulomatous dermatitis to the red dye within a tattoo that histologically resembled granuloma annulare. This is the first reported example of a perforating granuloma annulare-like reaction.

Omega-3 Polyunsaturated Fatty Acid Levels in Maternal and Cord Plasma Are Associated with Maternal Socioeconomic Status.

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother-infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys and maternal medical records. Mann-Whitney U tests and linear regression models were utilized for statistical analysis. Maternal eicosapentaenoic acid (EPA) (p = 0.02), cord EPA (p = 0.04), and total cord n-3 PUFA concentrations (p = 0.04) were significantly higher in college-educated mothers vs. mothers with less than a college education after adjustment for relevant confounders. Insurance type and household income were not significantly associated with n-3 or n-6 PUFA plasma concentrations after adjustment. Our findings suggest that mothers with lower educational status may be at risk of lower plasma concentrations of n-3 PUFAs at delivery, which could confer increased susceptibility to adverse pregnancy and birth outcomes.

Retinol and Pro-Vitamin A Carotenoid Nutritional Status during Pregnancy Is Associated with Newborn Hearing Screen Results.

The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother-infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC-MS/MS. NHS results were obtained from medical records. Statistical analysis utilized Mann-Whitney U tests and logistic regression models, with p ≤ 0.05 considered statistically significant. Abnormal NHS results were observed in 8.5% of infants. Higher median cord retinol (187.4 vs. 162.2 µg/L, p = 0.01), maternal trans-ß-carotene (206.1 vs. 149.4 µg/L, p = 0.02), maternal cis-ß-carotene (15.9 vs. 11.2 µg/L, p = 0.02), and cord trans-ß-carotene (15.5 vs. 8.0 µg/L, p = 0.04) were associated with abnormal NHS. Significant associations between natural log-transformed retinol and ß-carotene concentrations and abnormal NHS results remained after adjustment for smoking status, maternal age, and corrected gestational age. Further studies should investigate if congenital metabolic deficiencies, pesticide contamination of carotenoid-rich foods, maternal hypothyroidism, or other variables mediate this relationship.

A single GATA factor plays discrete, lineage specific roles in ascidian heart development.

GATA family transcription factors are core components of the vertebrate heart gene network. GATA factors also contribute to heart formation indirectly through regulation of endoderm morphogenesis. However, the precise impact of GATA factors on vertebrate cardiogenesis is masked by functional redundancy within multiple lineages. Early heart specification in the invertebrate chordate Ciona intestinalis is similar to that of vertebrates but only one GATA factor, Ci-GATAa, is expressed in the heart progenitor cells and adjacent endoderm. Here we delineate precise, tissue specific contributions of GATAa to heart formation. Targeted repression of GATAa activity in the heart progenitors perturbs their transcriptional identity. Targeted repression of endodermal GATAa function disrupts endoderm morphogenesis. Subsequently, the bilateral heart progenitors fail to fuse at the ventral midline. The resulting phenotype is strikingly similar to cardia bifida, as observed in vertebrate embryos when endoderm morphogenesis is disturbed. These findings indicate that GATAa recapitulates cell-autonomous and non-cell-autonomous roles performed by multiple, redundant GATA factors in vertebrate cardiogenesis.

A reemerging political space for linking person and community through primary health care.

OBJECTIVES: We sought to understand how national policy key informants perceive the value and changing role of primary care in the context of emerging political opportunities. METHODS: We conducted 13 semistructured interviews in May 2011 with leaders of federal agencies, think tanks, nonprofits, and quality standard-defining organizations with influence over health care reform policies and implementation. We recorded the interviews and used an editing and immersion-crystallization analysis approach to identify themes. RESULTS: We identified 4 themes: (1) affirmation of primary care as the foundation of a more effective health care system, (2) the patient-centered medical home as a transitional step to foster practice innovation and payment reform, (3) the urgent need for an increased focus on community and population health in primary care, and (4) the ongoing need for advocacy and research efforts to keep primary care on public and policy agendas. CONCLUSIONS: Current efforts to reform primary care are only intermediate steps toward a system with a greater focus on community and population health. Transformed and policy-enabled primary care is an essential link between personalized care and population health.

COVID-19 and Clinical Pastoral Education: How ACPE Educators Pivoted Amid the Pandemic.

Clinical Pastoral Education (CPE) programs faced extraordinary challenges during the COVID-19 pandemic. We examined how ACPE-certified educators responded to maintain program delivery. Survey results (n = 210) suggested a substantial and abrupt increase in remote delivery for CPE instruction and supervised clinical practice, primarily driven by those previously fully in-person. Respondents reported abrupt changes impacted 1152 students. Participants rated their utilization and helpfulness of professional, organizational, and technology resources during the pivot and beyond.

Assessing unmet rehabilitation needs and the feasibility of a telehealth rehabilitation consultation service for road trauma survivors recently discharged from hospital.

PURPOSE: Persistent activity limitations are common among road trauma survivors, yet access to rehabilitation in hospital and in the community remains variable. This study aimed to identify unmet rehabilitation needs following road trauma and assess the feasibility of a novel rehabilitation consultation service delivered via telehealth following hospitalization. METHODS: A pilot cohort study was conducted with survivors of road trauma who were hospitalized but did not receive formal inpatient rehabilitation. All participants received a multidisciplinary rehabilitation consultation via telehealth 1-3 weeks post-discharge, to assess rehabilitation needs and initiate treatment referrals as required. Functional and qualitative outcomes were assessed at baseline (1-7 days); one month and three months post-discharge. RESULTS: 38 participants were enrolled. All (100%) reported functional limitations at baseline; 86.5% were found to have unmet rehabilitation needs, and 75.7% were recommended rehabilitation interventions. Functional ability improved over time, but more than half the cohort continued to report activity limitations (67.6%), pain (64.7%) and/or altered mood (41.2%) for up to three months. Participants found the telehealth service to be acceptable, convenient, and helpful for recovery. CONCLUSIONS: A high proportion of mild-moderate trauma survivors report unmet rehabilitation needs following hospital discharge. Telehealth appears to be a feasible, convenient and acceptable mode of assessing these needs.Implications for rehabilitationSurvivors of road-related injuries often experience ongoing impairments and activity limitations.Among those who don't receive rehabilitation in hospital, we found a high proportion (86.5%) had unmet rehabilitation needs after discharge.A telehealth rehabilitation service was feasible to deliver and could successfully identify unmet rehabilitation needs.The piloted telehealth intervention was viewed as acceptable, convenient and beneficial by patients.

Delivering Clinical Pastoral Education (CPE) Remotely: Educators' Views and Perspectives During the COVID-19 Pandemic and Beyond.

Many Clinical Pastoral Education programs pivoted to remote delivery during the COVID-19 pandemic. Our survey explored educators' preparedness, self-efficacy, and views regarding remote Clinical Pastoral Education. Few respondents were either very (14.2%) or not at all (16.5%) prepared. Most were confident facilitating remote learning (69.8%-88.5%), believing remote Clinical Pastoral Education can achieve outcomes equivalent to in-person (59.1%). Six qualitative themes emerged: educator development, educator challenges, remote Clinical Pastoral Education efficacy, remote group dynamics, clinical practice/supervision implications, and benefits and opportunities.

Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis.

Several meiotic processes ensure faithful chromosome segregation to create haploid gametes. Errors to any one of these processes can lead to zygotic aneuploidy with the potential for developmental abnormalities. During prophase I of Drosophila male meiosis, each bivalent condenses and becomes sequestered into discrete chromosome territories. Here, we demonstrate that two predicted condensin II subunits, Cap-H2 and Cap-D3, are required to promote territory formation. In mutants of either subunit, territory formation fails and chromatin is dispersed throughout the nucleus. Anaphase I is also abnormal in Cap-H2 mutants as chromatin bridges are found between segregating heterologous and homologous chromosomes. Aneuploid sperm may be generated from these defects as they occur at an elevated frequency and are genotypically consistent with anaphase I segregation defects. We propose that condensin II-mediated prophase I territory formation prevents and/or resolves heterologous chromosomal associations to alleviate their potential interference in anaphase I segregation. Furthermore, condensin II-catalyzed prophase I chromosome condensation may be necessary to resolve associations between paired homologous chromosomes of each bivalent. These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon. We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors. Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

Natural Recovery by the Liver and Other Organs after Chronic Alcohol Use.

Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology states that a person who drinks alcohol excessively has alcohol use disorder. The liver is especially susceptible to alcohol-induced damage. This review summarizes and describes the effects of chronic alcohol use not only on the liver, but also on other selected organs and systems affected by continual heavy drinking-including the gastrointestinal tract, pancreas, heart, and bone. Most significantly, the recovery process after cessation of alcohol consumption (abstinence) is explored. Depending on the organ and whether there is relapse, functional recovery is possible. Even after years of heavy alcohol use, the liver has a remarkable regenerative capacity and, following alcohol removal, can recover a significant portion of its original mass and function. Other organs show recovery after abstinence as well. Data on studies of both heavy alcohol use among humans and animal models of chronic ethanol feeding are discussed. This review describes how (or whether) each organ/tissue metabolizes ethanol, as metabolism influences the organ's degree of injury. Damage sustained by the organ/tissue is reviewed, and evidence for recovery during abstinence is presented.

Contrasting Effects of Fasting on Liver-Adipose Axis in Alcohol-Associated and Non-alcoholic Fatty Liver.

Background: Fatty liver, a major health problem worldwide, is the earliest pathological change in the progression of alcohol-associated (AFL) and non-alcoholic fatty liver disease (NAFL). Though the causes of AFL and NAFL differ, both share similar histological and some common pathophysiological characteristics. In this study, we sought to examine mechanisms responsible for lipid dynamics in liver and adipose tissue in the setting of AFL and NAFL in response to 48 h of fasting. Methods: Male rats were fed Lieber-DeCarli liquid control or alcohol-containing diet (AFL model), chow or high-fat pellet diet (NAFL model). After 6-8 weeks of feeding, half of the rats from each group were fasted for 48 h while the other half remained on their respective diets. Following sacrifice, blood, adipose, and the liver were collected for analysis. Results: Though rats fed AFL and NAFL diets both showed fatty liver, the physiological mechanisms involved in the development of each was different. Here, we show that increased hepatic de novo fatty acid synthesis, increased uptake of adipose-derived free fatty acids, and impaired triglyceride breakdown contribute to the development of AFL. In the case of NAFL, however, increased dietary fatty acid uptake is the major contributor to hepatic steatosis. Likewise, the response to starvation in the two fatty liver disease models also varied. While there was a decrease in hepatic steatosis after fasting in ethanol-fed rats, the control, chow and high-fat diet-fed rats showed higher levels of hepatic steatosis than pair-fed counterparts. This diverse response was a result of increased adipose lipolysis in all experimental groups except fasted ethanol-fed rats. Conclusion: Even though AFL and NAFL are nearly histologically indistinguishable, the physiological mechanisms that cause hepatic fat accumulation are different as are their responses to starvation.