Unique report of iliocaval endovascular reconstruction successfully enabling a kidney transplant.

End-stage renal disease patients with Iliocaval venous obstruction are normally nom viable recipients for kidney transplantation. We report a case of a 34-year-old male patient in hemodialysis as renal replacement therapy for six years due to IgA nephropathy. Past medical history included multiple central venous catheter infections and catheter associated thrombosis. Iliac confluence and inferior vena cava occlusion previously excluded the patient from the renal transplantation list. Exhaustion of venous access sites was already previously documented. After multidisciplinary discussion the patients was proposed to endovascular Iliocaval reconstruction aiming a future kidney transplant. Iliocaval recanalization was achieved through bilateral femoral access. Inferior vena cava and iliac angioplasty were performed. A dedicated venous stent was deployed in the inferior vena cava, followed by a double-barrel reconstruction of the iliac confluence. Successful iliocaval recanalization was accomplished. Five months after kidney transplantation was performed with a deceased-donor graft in the right iliac fossa. Post operative period was uneventful. After 12 months the patient remained free from kidney replacement therapies with a serum creatinine of 1.3mg/dL. At the best of our knowledge this is the first clinical description of successful kidney transplant in a patient with a previous iliocaval reconstruction.

Pathophysiological Implications of Interstitial Cajal-like Cells (ICC-like) in Uterus: A Comparative Study with Gastrointestinal ICCs.

The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a "pacemaker" cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with contractile activity and c-Kit+ immunohistochemistry shared with ICCs. Among the locations where ICC-like cells have been observed, it is in the uterus where they have a significant functional and pathophysiological role. These cells are involved in obstetric phenomena of contractile action, such as ascending sperm transport, embryo implantation, pregnancy, delivery, and the expulsion of menstrual debris. Within the pathophysiology related to these cells, we find obstetric alterations such as recurrent miscarriages, premature deliveries, abolition of uterine contractions, and failures of embryo implantation, in addition to other common conditions in the fertile age, such as endometriosis and leiomyoma.

Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS-with predominant atrophy, muscle weakness, and fasciculations-and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients' prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.

Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress.

The enteric nervous system (ENS) is organized into two plexuses-submucosal and myenteric-which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut.

Influence of Mycoplasma hyopneumoniae natural infection on the respiratory microbiome diversity of finishing pigs.

Mycoplasma (M.) hyopneumoniae interacts with the respiratory microbiota and facilitates colonization of other pathogens. The present study investigated the pulmonary and nasal microbiota of M. hyopneumoniae-infected and M. hyopneumoniae-free pigs. Sixty-six pigs from three commercial herds were selected at the end of the finishing phase: 44 originated from two M. hyopneumoniae-positive herds and 22 from a M. hyopneumoniae-negative farm. At the slaughterhouse, samples of nasal turbinate (NT) and bronchus-alveolar lavage fluid (BALF) were collected. DNA was extracted with a commercial kit and the infection status was confirmed by qPCR. All samples from the same herd were pooled, and next-generation sequencing based on the hypervariable region V3-V4 of the 16 s bacterial rDNA was performed. Data analysis included the taxonomic analysis, Alpha diversity indexes, and Principal coordinates analysis (Pcoa) using Jaccard, Bray-Curtis, Weighted Unifrac, and Unweighted Unifrac distances. All pigs from the infected herds tested PCR positive for M. hyopneumoniae, whereas all pigs from the negative farm were negative. There was a greater diversity of microorganisms in BALF when compared to NT samples in all the farms. BALF samples from infected animals showed higher abundance of M. hyopneumoniae than NT samples and a predominance of Pasteurella multocida among the main species identified, which was also abundant in the M. hyopneumoniae-free herd. PCoa diagrams indicated that for most of the samples, dissimilarity on bacterial composition was observed, regardless of infection status and sample type. Therefore, the lung microbiota was modulated by M. hyopneumoniae infection, which could play a role in the pathogenesis of M. hyopneumoniae-disease.

Perception of animal welfare and its certification system by Brazilian consumers and dairy farmers.

The practices adopted in dairy farms can positively or negatively affect the perception of consumers. To meet consumer expectations and improve the productivity of dairy farms, a welfare certification system has recently been initiated in Brazil. In this research communication we describe the perceptions of Brazilian consumers and farmers regarding the implementation of welfare certification systems and the most common practices that affect animal welfare on dairy farms. For this purpose, two semi-structured questionnaires were used: one applied to 409 consumers and the other to 158 dairy farmers. The results demonstrate that consumers are concerned with the adoption of welfare practices in animal husbandry at dairy farms, mainly on topics related to movement restriction and cow-calf separation. Thus, the majority of consumers state that they are willing to pay more for welfare-certified dairy products. In addition, most dairy farmers are interested in adopting a welfare certification system, especially if it could add value to the raw milk sold to industries. Veterinarians and animal scientists are important for disseminating animal welfare recommendations, and the consequences of its improper adoption need to be emphasized. Finally, dairy farms need improvements regarding environmental hygiene, thermal conditions, animal husbandry, health, and milking processes. In conclusion, consumers and farmers are interested in welfare systems and their certification, and there is a need for stakeholders to make welfare certification a reality in the Brazilian dairy supply chain.

Performance of Commercial Mycoplasma hyopneumoniae Serum Enzyme-Linked Immunosorbent Assays under Experimental and Field Conditions.

Mycoplasma hyopneumoniae is an economically significant pathogen of swine. M. hyopneumoniae serum antibody detection via commercial enzyme-linked immunosorbent assays (ELISAs) is widely used for routine surveillance in commercial swine production systems. Samples from two studies were used to evaluate assay performance. In study 1, 6 commercial M. hyopneumoniae ELISAs were compared using serum samples from 8-week-old cesarean-derived, colostrum-deprived (CDCD) pigs allocated to the following 5 inoculation groups of 10 pigs each: (i) negative control, (ii) Mycoplasma flocculare (strain 27399), (iii) Mycoplasma hyorhinis (strain 38983), (iv) Mycoplasma hyosynoviae (strain 34428), and (v) M. hyopneumoniae (strain 232). Weekly serum and daily oral fluid samples were collected through 56 days postinoculation (dpi). The true status of pigs was established by PCR testing on oral fluids samples over the course of the observation period. Analysis of ELISA performance at various cutoffs found that the manufacturers' recommended cutoffs were diagnostically specific, i.e., produced no false positives, with the exceptions of 2 ELISAs. An analysis based on overall misclassification error rates found that 4 ELISAs performed similarly, although one assay produced more false positives. In study 2, the 3 best-performing ELISAs from study 1 were compared using serum samples generated under field conditions. Ten 8-week-old pigs were intratracheally inoculated with M. hyopneumoniae Matched serum and tracheal samples (to establish the true pig M. hyopneumoniae status) were collected at 7- to 14-day intervals through 98 dpi. Analyses of sensitivity and specificity showed similar performance among these 3 ELISAs. Overall, this study provides an assessment of the performance of current M. hyopneumoniae ELISAs and an understanding of their use in surveillance.

Epidemiology of bovine cysticercosis and associated economic losses in the state of Rio Grande do Sul, Brazil.

Bovine cysticercosis (BCC) is the most frequently detected zoonosis in Brazilian slaughterhouses and is considered a problem for public health and beef production chain, requiring epidemiological studies focusing on evaluating its prevalence, spatial distribution, and economic losses in order to improve and adopt specific strategies for BCC control. Thus, this study focused to establish BCC prevalence and spatial distribution in the state of Rio Grande do Sul, Brazil, and estimate the economic losses for cattle farmers suppliers of one exporter slaughterhouse. A set of 70,591 bovine carcasses were postmortem inspected from 2019 to 2020, which came from 134 municipalities located in eight distinct regions in the state of Rio Grande do Sul. The prevalence found was 3.44% (C.I. 95% 3.30-3.57%), and animals infected with unviable cysticerci were more frequently detected (70.56%) than those carrying viable ones (29.44%). The most frequent destination of carcasses and viscera was non-export (65.48%), followed by freezing/salting (25.41%), heat treatment (8.74%), and rendering (0.37%), resulting in a total economic burden of at least US$ 167,868.53 for cattle farmers. Some regions had higher risk for BCC occurrence, such as Porto Alegre, Caxias do Sul, Santa Maria, Ijuí, and Passo Fundo (OR > 1, p < 0.05), respectively. These results highlight the need of adopting prophylactic measures, mainly in specific areas, in order to control BCC and reduce the economic losses for beef production chain.

Cross-sectional study of Leptospira spp. in commercial pig farms in the state of Goiás, Brazil.

Leptospirosis is an infectious, contagious disease highly important to the world pig industry, which causes reproductive loss in breeding herds. Endemic infections in a herd may produce little evidence of clinical disease despite resulting in economic losses. However, some epidemiological features of leptospirosis in midwestern Brazil, such as risk factors and prevalence of the disease, remain unclear. Therefore, this study focused on assessing the prevalence of the Leptospira spp. in intensive pig herds and associating its risk factors. A set of 900 blood samples, equally distributed between nursery, growing, and finishing pigs of 30 intensive farrow-to-finish farms, were analyzed using the microagglutination test (MAT), in order to detect anti-Leptospira spp. antibodies for 24 different Leptospira spp. serovars. An occurrence of 4.67% (55/342) seropositive samples were detected in fattening pigs. The variables associated with the disease occurrence were animals per square meter at fattening (OR 0.006, CI 95% 0.004-0.42, p = 0.0105) and pen division between growing and fattening pigs (OR 3.56, CI 95% 0.563-22.541, p = 0.185). Thus, the variables semi-hollow floor in the maternity (OR 16.66; CI 95%: 2.17-128.2 and p = 0.006) and animals per trough at fattening (OR: 0.08, CI 95% 0.009-0.87 and p = 0.025), observed in this study, highlight the importance of the fattening phase in the epidemiology of the disease, bringing information on risk factors involved in the occurrence and dissemination of leptospirosis in intensive pig herds.

Peripherally administered melanocortins induce mice fat browning and prevent obesity.

BACKGROUND/OBJECTIVES: The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. METHODS: The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. RESULTS: Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. CONCLUSIONS: This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.

Description of risk factors associated with the detection of BVDV antibodies in Brazilian pig herds.

Bovine viral diarrhea virus (BVDV) infects ruminants as primary hosts. However, other animals like pigs are susceptible. This study was conducted to investigate seroprevalence and risk factors associated with the detection of BVDV antibodies in pig herds. A total of 1.705 serum samples of 33 finisher herds, from seven Brazilian states, were collected in slaughterhouses. The samples were tested by virus neutralization (VN) test. In total, 5.35% (91/1.705) were positive and 64% (21/33) of the herds had positive animals. A significant association with "trucks are not cleaned and disinfected" and "visitors do not respect 72-h interval between visits to farms" (P < 0.05) was found in association with detection of BVDV-2 antibodies. This study suggests that important biosecurity gaps are present in Brazilian pig farms, as the presence of BVDV antibodies in pigs suggests (direct or indirect) contact with population(s) of ruminant species. Closing biosecurity gaps prevents spread of BVDV and other pathogens such as foot-and-mouth disease virus (FMDV) between pig and ruminant farms. This data should be taken in account by CSF surveillance programs, once cross-reaction in serologic tests between classical swine fever virus (CSFV) and BVDV antibodies has been shown to occur.

A cross-sectional study of swine influenza in intensive and extensive farms in the northeastern region of the state of São Paulo, Brazil.

Swine influenza (SI) is a seasonal infectious disease highly important to the world pig industry. Loss of daily weight gain, increased costs for the prevention and treatment of secondary infections are the main economic losses associated with the presence of this disease. However, some epidemiological features of SI remain quite unclear. This study focused on assessing the prevalence of swine influenza virus (SIV) infection in intensive and extensive pig herds and associating risk factors. A set of 601 blood samples of five intensive farrow-to-finish farms and 361 blood samples from 56 extensive farms were analyzed using an indirect ELISA kit CIVTEST SUIS INFLUENZA®, Hipra (Amer, Spain), in order to detect anti-SIV antibodies. In total, 24.13 % of samples from intensive herds were positive, while no positive samples were detected in extensive rearing herds. Sow and weaning piglets had the highest prevalence values. In the intensive rearing system, occurrence of reproductive disorders and exposure to recently introduced animals were positively associated with the disease occurrence in swine herds. The findings highlight the importance of sows in the epidemiology of the disease and bring information about risk factors involved in the occurrence of swine influenza in intensive herds.

Intracellular signaling mechanisms of the melanocortin receptors: current state of the art.

The melanocortin system is composed by the agonists adrenocorticotropic hormone and α, ß and γ-melanocyte-stimulating hormone, and two naturally occurring antagonists, agouti and agouti-related protein. These ligands act by interaction with a family of five melanocortin receptors (MCRs), assisted by MCRs accessory proteins (MRAPs). MCRs stimulation activates different signaling pathways that mediate a diverse array of physiological processes, including pigmentation, energy metabolism, inflammation and exocrine secretion. This review focuses on the regulatory mechanisms of MCRs signaling, highlighting the differences among the five receptors. MCRs signal through G-dependent and independent mechanisms and their functional coupling to agonists at the cell surface is regulated by interacting proteins, namely MRAPs and ß-arrestins. The knowledge of the distinct modulation pattern of MCRs signaling and function may be helpful for the future design of novel drugs able to combine specificity, safety and effectiveness in the course of their therapeutic use.

A new tropane alkaloid from the leaves of Erythroxylum subsessile isolated by pH-zone-refining counter-current chromatography.

Tropane alkaloids are bioactive metabolites with great importance in the pharmaceutical industry and the most important class of natural products found in the Erythroxylum genus. However, these compounds are usually separated by traditional chromatographic techniques, in which the sample is progressively purified in multiple chromatographic steps, resulting in a time- and solvent-consuming procedure. In this work we present the isolation of a novel alkaloid, 6ß,7ß-dibenzoyloxytropan-3α-ol, together with the two known 3α-benzoyloxynortropan-6ß-ol and 3α,6ß-dibenzoyloxytropane alkaloids, directly from the crude alkaloid fraction from the leaves of Erythroxylum subsessile, by using a single run pH-zone-refining counter-current chromatography method. The ethyl acetate/water (1:1, v/v) biphasic solvent system with triethylamine and HCl as retention and eluter agents, respectively, was used to isolate tropane alkaloids for the first time. The structures of the isolated alkaloids were elucidated by spectroscopic methods.

Antioxidant Supplementation Modulates Age-Related Placental Bed Morphology and Reproductive Outcome in Mice.

The number of women who delay their first childbirth is increasing. This demographic shift is an important health issue because advanced maternal age is a risk factor for reproductive capacity loss and the occurrence of placental bed disorders that may lead to placenta abruption, preeclampsia, and placenta insufficiency. A redox imbalance status, resulting from the enhanced production of reactive oxygen species or their deficient neutralization, is proposed to occur in this setting. Thus, uterine redox status was evaluated in young (8- to 12-wk-old) and reproductively aged (38- to 42-wk-old) mice. In addition, it was hypothesized that specific dietary antioxidant supplementation would restore the balance and improve the reproductive outcome of aging female mice. To test this hypothesis, two different antioxidants, the nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor apocynin and the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL), were added to the drinking water of female mice prior to and during pregnancy. Compared to younger females, uteri from reproductively aged nonpregnant mice exhibited areas of endometrial cystic dilation, increased level of NOX1 expression, and enhanced protein carbonylation, especially in the apical surface of the luminal epithelium. Both antioxidants decreased protein carbonylation level in the uterus of reproductively aged mice. When reproductively aged females became pregnant, the litter size was smaller and fetuses were heavier. The change was accompanied by a significant decrease in decidua thickness. Provision of apocynin significantly increased litter size and restored decidua thickness. Reproductively aged mice provided with TEMPOL did not evidence such benefits, but whereas apocynin normalized fetal birth weight, TEMPOL further increased it. These findings emphasize that uterine redox balance is important for reproductive success and suggest that age-related redox imbalance might be compensated by specific antioxidant supplementation.

Relationship between body mass index and mean arterial pressure in normotensive and chronic hypertensive pregnant women: a prospective, longitudinal study.

BACKGROUND: Being overweight is associated with both higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) during pregnancy and increased risk of gestational hypertensive disorders. The objective of this study was to determine and quantify the effect of body mass index (BMI) on mean arterial pressure (MAP) at several time points throughout pregnancy in normotensive (NT) and chronic hypertensive pregnant (HT) women. METHODS: A prospective longitudinal study was carried out in 461 singleton pregnancies (429 low-risk and 32 with chronic arterial hypertension), with measurements taken at the 1(st), 2(nd), and 3(rd) trimesters and at delivery. Linear mixed-effects regression models were used to evaluate the time-progression of BMI, SBP, DBP and MAP during pregnancy (NT vs. HT). The longitudinal effect of BMI on MAP, adjusted for the hypertensive status, was investigated by the same methodology. RESULTS: BMI consistently increased with time in both NT and HT women. In contrast, MAP decreased during the first half of pregnancy, after which it increased until the moment of delivery in both groups. A 5-unit increase in BMI was predicted to produce an increase of approximately 1 mmHg in population MAP values. This effect is independent from the time period and from hypertensive status. CONCLUSIONS: In both NT and HT pregnant women, MAP is strongly (and significantly) influenced by increases in BMI.

Uterine artery Doppler in the management of early pregnancy loss: a prospective, longitudinal study.

BACKGROUND: The pharmacological management of early pregnancy loss reduced substantially the need for dilation and curettage. However, prognostic markers of successful outcome were not established. Thus the major purpose of this study was to determine the sensitivity and specificity of the uterine artery pulsatility (PI) and resistance (RI) indices to detect early pregnancy loss patients requiring dilation and curettage after unsuccessful management. METHODS: A cohort prospective observational study was undertaken to include women with early pregnancy loss, ≤ 12 weeks of gestation, managed with mifepristone (200 mg) and misoprostol (1600 µg) followed by PI and RI evaluation of both uterine arteries 2 weeks after. At this time, in 173/315 patients, incomplete miscarriage was diagnosed. Among them, 32 underwent uterine dilatation and curettage at 8 weeks of follow-up. RESULTS: The cut-off points for the uterine artery PI and RI, leading to the maximum values of sensitivity (69.5%, CI95%: 61.5%-76.5% and 75.0%, CI95%: 57.9%-86.8%, respectively) and specificity (75.0%, CI95%: 57.9%-86.8% and 65.6%, CI95%: 48.3%-79.6%, respectively), for the discrimination between the women who needed curettage from those who resolved spontaneously were 2.8 and 1, respectively. CONCLUSIONS: The potential usefulness of uterine artery Doppler evaluation to predict the need for uterine curettage in patients submitted to medical treatment for early pregnancy loss was demonstrated.

Uterine artery impedance during puerperium in normotensive and chronic hypertensive pregnant women.

PURPOSE: The present study compared the Doppler flow pulsatility indices (PI) in the uterine arteries (UtA) during the puerperium between healthy women and those with stage-1 essential hypertension who had uncomplicated pregnancies and delivered by elective caesarean section. The change in the mean arterial pressure (MAP) and body mass index (BMI) over time was also assessed. METHODS: A longitudinal and prospective study was performed in singleton pregnancies of 28 normotensive (NT) and 24 hypertensive (HT) women. The UtA-PI was measured immediately before caesarean section (time 0) and at 1 week (time 1) and 4 weeks (time 2) postpartum. The presence or absence of early diastolic notches was recorded. The change in the MAP, BMI, and UtA-PI over time and between the two populations was modelled through multivariate linear regression using the generalised least squares. RESULTS: In both groups, the UtA-PI significantly increased from time 0 to time 1 (p < 0.05) and time 2 (p < 0.05). Stage-1 hypertension did not change the trend but did increase the UtA-PI magnitude (p < 0.05). The presence of uterine artery notching increased over time, from 6 to 98%, in both groups (p < 0.001); however, in the HT group, at time 1, the majority of women exhibited positive notching [92% (HT) vs 57% (NT), p = 0.013]. CONCLUSIONS: Chronic stage-1 hypertensive women with normal pregnancy outcomes exhibited a progressively increasing postpartum UtA impedance. This trend also occurred in normotensive women, albeit at a significantly lower magnitude.

Alpha-MSH signalling via melanocortin 5 receptor promotes lipolysis and impairs re-esterification in adipocytes.

The melanocortin system has a clear effect on the mobilisation of stored lipids in adipocytes. The aim of the current study was to investigate the role of melanocortin 5 receptor (MC5R) on alpha-melanocyte-stimulating hormone (alpha-MSH)-induced lipolysis in 3T3-L1 adipocytes. To this end, MC5R expression was decreased by small interfering RNA (siRNA), which significantly impaired the alpha-MSH stimulation of lipolysis, as determined by glycerol and nonesterified fatty-acid (NEFA) quantification. The functional role of alpha-MSH/MC5R on triglyceride (TG) hydrolysis was mediated by hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), perilipin 1 (PLIN1) and acetyl-CoA carboxylase (ACC). Immunofluorescence microscopy revealed that phosphorylated HSL clearly surrounded lipid droplets in alpha-MSH-stimulated adipocytes, whereas PLIN1 left the immediate periphery of lipids. These observations were lost when the expression of MC5R was suppressed. In 3T3-L1 adipocytes, alpha-MSH-activated MC5R signals through the cAMP/PKA and MAPK/ERK1/2 pathways. PKA was fundamental for HSL and PLIN1 activation and lipolysis regulation. ERK1/2 inhibition strongly interfered with the release of NEFAs but not glycerol. In addition, the intracellular TG levels, which were decreased after MC5R activation, were restored after ERK1/2 inhibition, indicating that these kinases are involved in NEFA re-esterification rather than lipolysis regulation. This notion is also supported by the observation that the alpha-MSH-mediated activation of phosphoenolpyruvate carboxykinase (PEPCK) was abolished in the presence of ERK1/2 inhibitors. Altogether, these results indicate that alpha-MSH-activated MC5R regulates two tightly coupled pathways in adipocytes: lipolysis and re-esterification. The global effect is a decrease in adipocyte fat mass, which is important for strategies to ameliorate obesity.