Group of Children South Normanby

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOUnder physiological conditions, the brain consumes over 20% of the whole body energy supply. The blood-brain barrier (BBB) allows dynamic interactions between blood capillaries and the neuronal network in order to provide an adequate control of molecules that are transported in and out of the brain. Alterations in the BBB structure and function affecting brain accessibility to nutrients and exit of toxins are found in a number of diseases, which in turn may disturb brain function and nutrient signaling. In this review we explore the major advances obtained in the understanding of the BBB development and how its structure impacts on function. Furthermore, we focus on the particularities of the barrier permeability in the hypothalamus, its role in metabolic control and the potential impact of hypothalamic BBB abnormities in metabolic related diseases2111112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã

Passiflora edulis peel intake improves insulin sensitivity, increasing incretins and hypothalamic satietogenic neuropeptide in rats on a high-fat diet

This study aimed to investigate the effect of Passiflora edulis peel flour (PEPF) intake on hypothalamic neuropeptides messenger RNA expression, insulin sensitivity, and other metabolic parameters in Sprague-Dawley rats fed a high-fat (HF) diet. Methods: Sprague-Dawley rats were divided in 3 groups: a control group, fed on a normal fat diet; a HF group, fed on a high-fat diet (35% fat [w/w]); and a high-fat Passiflora flour (HFPF) group, fed on a HF diet containing PEPF. The rats from the HFPF group as well as the HF group were kept on an HF diet for the first 4 wk to induce metabolic conditions related to obesity. Then the HFPF group was switched to a HF diet containing PEPF for additional 6 wk. Other groups were kept on normal-fat and HF diet without addition of PEPF during the whole period of experiment. The glucose tolerance and insulin sensitivity were evaluated through the glucose tolerance test (GTT) and the insulin tolerance test (ITT). Gut hormones and adipokines were measured through an immunoassay. The hypothalamic neuropeptides expression was assessed by real-time polymerase chain reaction. Results: The PEPF intake increased the hypothalamic cocaine- and amphetamine-regulated transcript expression (CART) (P < 0.05), counteracted cumulative body weight gain (P < 0.001), decreased adiposity (P < 0.05) and leptin level (P < 0.01), whereas increased adiponectin (P < 0.01), glucose-dependent insulinotropic polypeptide (P < 0.01), and glucagon-like peptide-1 (GLP-1) (P < 0.001) improved the insulin sensitivity in diet-induced obesity rats by increasing the kITT (glucose disappearance rate) (P < 0.01), which was calculated during the ITT. Other gut hormones (peptide tyrosine tyrosine, pancreatic polypeptide, and amylin) and interleukins (IL) (IL-6, tumor necrosis factor-α, IL-1β, and monocyte chemoattractant protein-1) were not changed by the PEPF intake. Conclusion: Our findings provide a further understanding of how the PEPF works as a dietary component to improve glucose homeostasis and demonstrate a molecular mechanism that may increase satiety by PEPF in diet-induced obesity.327-8863870CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação2012/12322-

Jaboticaba peel extract decrease autophagy in white adipose tissue and prevents metabolic disorders in mice fed with a high-fat diet

The increase in autophagy markers in the white adipose tissue is associated with adipocyte hypertrophy and obesity physiopathology. The jaboticaba peel is rich in bioactive compounds as polyphenols, which have been demonstrating anti-oxidant and inflammatory effects, and possibly interferes in adipose tissue metabolism and obesity. Thus, this study aimed to evaluate the effects of jaboticaba peel extract (FJE) treatment in autophagy markers of epididymal and inguinal white adipose tissue (eWAT and iWAT) of mice fed a normocaloric or high-fat diet for 6 weeks. The FJE treatment modulates autophagy markers in the eWAT of animals fed a high-fat diet by the reduction of Beclin-1 and LC3BII, and an increase in SQSTM-p62, accompanied by a decrease in tissue and total body weight, indicating the importance of autophagy in obesity development. These alterations were not followed by lower cytokines concentration, suggesting that autophagy may be fundamental to adipocyte remodeling at the beginning of adipocyte hypertrophy, before the onset of low-grade inflammation. Furthermore, the treatment reduced total serum triglycerides and liver fat accumulation. Thus, the results suggest that FJE could be considered a strategy against metabolic disorders caused by an HF diet.64147156CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP301108/2016-12015/20766-3 ; 2013/13480-0 ; 2015/50333-

Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation.

Current pharmacological therapies for treating obesity are of limited efficacy. Genetic ablation or loss of function of AMP-activated protein kinase alpha 1 (AMPKα1) in steroidogenic factor 1 (SF1) neurons of the ventromedial nucleus of the hypothalamus (VMH) induces feeding-independent resistance to obesity due to sympathetic activation of brown adipose tissue (BAT) thermogenesis. Here, we show that body weight of obese mice can be reduced by intravenous injection of small extracellular vesicles (sEVs) delivering a plasmid encoding an AMPKα1 dominant negative mutant (AMPKα1-DN) targeted to VMH-SF1 neurons. The beneficial effect of SF1-AMPKα1-DN-loaded sEVs is feeding-independent and involves sympathetic nerve activation and increased UCP1-dependent thermogenesis in BAT. Our results underscore the potential of sEVs to specifically target AMPK in hypothalamic neurons and introduce a broader strategy to manipulate body weight and reduce obesity