Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure.

BACKGROUND/OBJECTIVES: Stearoyl-CoA desaturase-2 (SCD2) is the main δ9 desaturase expressed in the central nervous system. Because of its potential involvement in controlling whole-body adiposity, we evaluated the expression and function of SCD2 in the hypothalami of mice. SUBJECTS/METHODS: Male mice of different strains were used in real-time PCR, immunoblot and metabolic experiments. In addition, antisense oligonucleotides and lentiviral vectors were used to reduce and increase the expression of SCD2 in the hypothalamus. RESULTS: The level of SCD2 in the hypothalamus is similar to other regions of the central nervous system and is ~10-fold higher than in any other region of the body. In the arcuate nucleus, SCD2 is expressed in proopiomelanocortin and neuropeptide-Y neurons. Upon high fat feeding, the level of hypothalamic SCD2 increases. Inhibition of hypothalamic SCD2 as accomplished by two distinct approaches, an antisense oligonucleotide or a short-hairpin RNA delivered by a lentivirus, resulted in reduced body mass gain mostly due to increased energy expenditure and increased spontaneous activity. Increasing hypothalamic SCD2 by a lentivirus approach resulted in no change in body mass and food intake. CONCLUSIONS: Thus, SCD2 is highly expressed in the hypothalami of rodents and its knockdown reduces body mass due to increased whole-body energy expenditure.

TNF-α transiently induces endoplasmic reticulum stress and an incomplete unfolded protein response in the hypothalamus.

In diet-induced obesity, hypothalamic inflammation is triggered as an outcome of prolonged exposure to dietary fats. Toll-like receptor 4 (TLR4) activation plays a central role in this process, inducing endoplasmic reticulum stress and activating inflammatory cytokine gene transcription. Although saturated fatty acids can induce endoplasmic reticulum stress in the hypothalamus, it is unknown whether inflammatory cytokines alone can activate this mechanism. Here, rats were treated with TNF-α or lyposaccharide (LPS) and endoplasmic reticulum stress and unfolded protein response were evaluated by immunoblot and polymerase chain reaction (PCR). Activation of TLR4 by LPS was capable of inducing a complete endoplasmic reticulum stress and unfolded protein response through the PERK/eIF2α and IRE1α/XBP1 pathways. Conversely, TNF-α, injected either locally or systemically, was unable to induce a complete program of unfolded protein response, although the activation of endoplasmic reticulum stress was achieved to a certain degree. Thus, in the hypothalamus, the isolated action of TNF-α is insufficient to produce the activation of a complete program of unfolded protein response.

Evaluation of Chagas' disease transmission through breast feeding

Foram estudadas, parasitologicamente, 100 amostras de leite ou colostro de 78 mäes chagásicas crônicas, através do exame direito e inoculaçäo em camundongos. Os animais foram submetidos a exame direito, três vezes por semana e, ao fim de 45 días, também, a xenodiagnóstico e a exame sorológico para pesquisa de anticorpos anti Trypanosoma cruzi. Näo houve evidência de parasitismo pelo T. cruzi nas amostras estudadas, muito embora em cinco mäes tivesse sido documentada parasitemia no momento da colheita do material. Foram, também, examinados, sorologicamente, através da pesquisa de anticorpos IgG anti-T. cruzi, filhos de chagásica crônicas, nos quais excluiu-se, ao nascer, infecçäo pelo T.cruzi. nestas crianças näo se comprovou infecçäo chagásica. Os autores concluem que näo se deve proibir a amamentaçäo nessas mäes, mas como apresentam parasitemia intermitente devem ser recomendadas a näo amamentar quando houver sangramento do mamilo