Fabiana Alves Neves

Ghrelin and leptin modulate the feeding behaviour of the hawksbill turtle Eretmochelys imbricata during nesting season

Female sea turtles rarely have been observed foraging during the nesting season. We investigated the levels of ghrelin, leptin and other physiological and nutritional parameters in nesting hawksbill sea turtles in Brazil. We found that levels of serum leptin (appetite-suppressing protein) decreased over the nesting season, while an increasing trend was observed in ghrelin (hunger-stimulating peptide). Both findings are consistent with the prediction that post-nesting females will begin to forage after the nesting season, , either during or just after their post-nesting migration.

Heart energy metabolism impairment in Western-diet induced obese mice

Nutritional transition has contributed to growing obesity, mainly by changing eating habits of the population. The mechanisms by which diet-induced obesity leads to cardiac injury are not completely understood, but it is known that obesity is associated to impaired cardiac function and energy metabolism, increasing morbidity and mortality. Therefore, our study aimed to investigate the mechanisms underlying cardiac metabolism impairment related to Western diet-induced obesity. After weaning, male Swiss mice were fed a Western diet for 16 weeks in order to induce obesity. After this period, the content of proteins involved in heart energy metabolism GLUT1, cytosolic lysate and plasma membrane GLUT4, AMPK, pAMPK, IRβ, IRS-1, PGC-1α, CPT1 and UCP2 was evaluated. Also, the oxidative phosphorylation of myocardial fibers was measured by high-resolution respirometry. Mice in the Western diet group (WG) presented altered biometric parameters compared to those in control group, including higher body weight, increased myocardial lipid deposition and glucose intolerance, which demonstrate the obesogenic role of Western diet. WG presented increased CPT1 and UCP2 contents and decreased IRS-1, plasma membrane GLUT4 and PGC-1α contents. In addition, WG presented cardiac mitochondrial dysfunction and reduced biogenesis, demonstrating a lower capacity of carbohydrates and fatty acid oxidation and also decreased coupling between oxidative phosphorylation and adenosine triphosphate synthesis. Cardiac metabolism impairment related to Western diet-induced obesity is probably due to damaged myocardial oxidative capacity, reduced mitochondrial biogenesis and mitochondria uncoupling, which compromise the bioenergetic metabolism of heart.

Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood

AIM In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRβ), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.

Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

Overnutrition during lactation leads to impairment in insulin signaling, up-regulation of GLUT1 and increased mitochondrial carbohydrate oxidation in heart of weaned mice.

Several studies have demonstrated that overnutrition during early postnatal period can increase the long-term risk of developing obesity and cardiac disorders, yet the short-term effects of postnatal overfeeding in cardiac metabolism remains unknown. The aim of our study was to investigate the cardiac metabolism of weaned mice submitted to overnutrition during lactation, particularly as to mitochondrial function, substrate preference and insulin signaling. Postnatal overfeeding was induced by litter size reduction in mice at postnatal day 3. At 21 days of age (weaning), mice in the overfed group (OG) presented biometric and biochemical parameters of obesity, including increased body weight, visceral fat, liver weight and increased left ventricle weight/tibia length ratio; indicating cardiac hypertrophy, hyperglycemia, hyperinsulinemia and increased liver glycogen content compared to control group. In the heart, we detected impaired insulin signaling, mainly due to decreased IRβ, pTyr-IRS1, PI3K, GLUT4 and pAkt/Akt and increased PTP1B, GLUT1 and pAMPKα/AMPKα content. Activities of lactate dehydrogenase and citrate synthase were increased, accompanied by enhanced carbohydrate oxidation, as observed by high-resolution respirometry. Moreover, OG hearts had lower CPT1, PPARα and increased UCP2 mRNA expression, associated with increased oxidative stress (4-HNE content), BAX/BCL2 ratio and cardiac fibrosis. Ultrastructural analysis of OG hearts demonstrated mild mitochondrial damage without alterations in OXPHOS complexes. In conclusion, overnutrition during early life induces short-term metabolic disturbances, impairment in heart insulin signaling, up-regulates GLUT-1 and switch cardiac fuel preference in juvenile mice.

Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice

Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRβ). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells.

Changes in body weight, C-reactive protein, and total adiponectin in non-obese women after 12 months of a small-volume, home-based exercise program

OBJECTIVE: Our objective was to evaluate the effects of small-volume, home-based exercise combined with slight caloric restriction on the inflammatory markers C-reactive protein and adiponectin. METHODS: In total, 54 women were randomly assigned to one of two groups for exercise intervention: the control or home-based exercise groups. Weight, waist and hip circumferences, and inflammatory markers were measured at baseline and after 6 and 12 months. Women allocated to the home-based exercise group received a booklet explaining the physical exercises to be practiced at home at least 3 times per week, 40 minutes per session, at low-to-moderate intensity. All participants received dietary counseling aimed at reducing caloric intake by 100-300 calories per day, with a normal distribution of macro-nutrients (26-28% of energy as fat). Clinicaltrials.gov: NCT01206413 RESULTS: The home-based exercise group showed a significantly greater reduction in weight and body mass index at six months, but no difference between groups was observed thereafter. With regard to the inflammatory markers, a greater but non-statistically significant reduction was found for C-reactive protein in the home-based exercise group at six months; however, this difference disappeared after adjusting for weight change. No differences in adiponectin were found at the 6- or 12-month follow-up. CONCLUSION: Small-volume, home-based exercise did not promote changes in inflammatory markers independent of weight change.

Appetite-related hormone levels in obese women with and without binge eating behavior

OBJETIVO: O objetivo deste estudo foi avaliar, antes e apos a refeicao, as concentracoes sericas de hormonios ligados ao controle do apetite (peptideo YY3-36, grelina total, leptina e insulina) em mulheres obesas com e sem episodios de compulsao alimentar e compara-las as mulheres de peso normal. METODOS: Vinte e cinco mulheres com idade entre 32 e 50 anos foram convidadas a participar deste estudo, incluindo 9 mulheres com peso normal (20-25kg/m2) sem episodios de compulsao alimentar (grupo 1), 9 mulheres obesas (³30 kg/m2) com episodios de compulsao alimentar (grupo 2) e 7 mulheres obesas sem episodios de compulsao alimentar (grupo 3). Foram coletadas quatro amostras de sangue pos-prandiais a 60 minutos (1 hora antes), bem como 15, 45 e 90 minutos apos uma refeicao composta de 55% de carboidratos, 15% de proteinas e 30% de lipideos. RESULTADOS: O maior HOMA-IR foi observado no grupo 3 (M=2,5, DP=1,04) quando comparado ao grupo 1 (M=1,5, DP=0,53) e ao grupo 2 (M=1,8, DP=0,58), p=0,04. O indice de massa corporal (p<0,0001), a leptina (p<0,0001) e a insulina (p=0,01) foram maiores no grupo 3 antes e apos a refeicao. A grelina total (p=0,003) e o PYY3-36 (p=0,02) foram menores no grupo 2 antes e apos a refeicao. Apos o ajuste do indice de massa corporal, apenas a baixa concentracao de PYY3-36 no grupo 2 manteve-se estatisticamente diferente entre os grupos (p=0,01). CONCLUSAO: Este estudo sugere que niveis baixos do PYY-3-36 estejam associados a compulsao alimentar em mulheres obesas.