Gold Nanoclusters Eliminate Obesity Induced by Antipsychotics

Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs’ good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity

Pengaruh Irisin pada Pencoklatan Lemak Putih

Pendahuluan: Irisin merupakan miokin baru yang menghubungkan aktivitas fisik yang berhubungan dengan peningkatan kinerja metabolisme dan berkaitanan dengan pencoklatan jaringan adiposa putih menjadi coklat. Tujuan: Mengetahui pengaruh irisin pada pencoklatan lemak putih. Metode: Menggunakan studi literatur dari sumber ilmiah dengan meringkas dari publikasi dan membandingkan hasil yang disajikan. Hasil: Irisin yang disekresikan dari otot, akan menstimulasi ekspresi dari uncoupling protein 1 (UCP1) dalam adiposit yang menyebabkan pencoklatan jaringan adiposa putih melalui p38 mitogen-activated protein kinase (MAPK) dan melalui extracellular-signal regulated kinase (ERK). Kesimpulan: Irisin yang disekresikan otot rangka akan mengekspresikan UPC-1 di jaringan adiposa yang menyebabkan jaringan adiposa putih menjadi coklat dan peningkatan aktivitas thermogenesis.

Proses Pencokelatan Jaringan Adiposa

Obesity is a common, serious, and detrimental condition. In 2014, more than 1.9 billion adults were overweight. Obesity is associated with many diseases and the increase in obesity has become a major health problem. Obesity is caused by an imbalance between energy intake and energy consumption. Adipose tissue is an endocrine organ that secretes many hormones and cytokines that can affect metabolism. There are two types of adipose tissue in the body with different functions, namely white adipose tissue and brown adipose tissue. White fat has a major function in storing energy and is increased in obesity, while brown fat produces heat (thermogenesis) and then increases energy consumption. Therefore, brown fat and the induction of brown fat-like properties in white fat, have been considered as targets in the fight against obesity. The complex process of cell differentiation leading to the appearance of active brown adipocytes has been identified. There are classic brown adipocytes and cream adipocytes. Beige adipocytes are brown adipocytes that appear on precursor cells of white adipose tissue due to stimuli. Brown adipocytes are equipped with mitochondria containing uncoupling protein 1 (UCP1), which, when activated, controls ATP synthesis and stimulates respiratory chain activity. The browning process of adipose tissue is controlled by factors such as exercise. Obesitas merupakan keadaan yang umum, serius, dan merugikan. Tahun 2014, lebih dari 1,9 milyar orang dewasa mengalami kelebihan berat badan. Obesitas berasosiasi dengan banyak penyakit dan peningkatan obesitas telah menjadi masalah kesehatan utama. Obesitas disebabkan oleh ketidakseimbangan antara energi yang masuk dan konsumsi energi. Jaringan adiposa dalam tubuh ada dua tipe yang fungsinya berbeda, yakni jaringan adiposa putih dan jaringan adiposa cokelat. Lemak putih berfungsi utama dalam menyimpan energi dan meningkat pada obesitas, sedangkan lemak cokelat menghasilkan panas (termogenesis) dan kemudian meningkatkan konsumsi energi. Oleh karena itu, lemak cokelat dan induksi sifat seperti lemak cokelat pada lemak putih, telah dipertimbangkan sebagai target dalam melawan obesitas. Tujuan penelitian ini adalah untuk mengetahui proses pencoklatan jaringan adiposa putih. Metode penelitian yang digunakan adalah metode penelusuran ilmiah. Hasil penelitian diperoleh bahwa adiposit krem merupakan adiposit cokelat yang muncul pada sel prekursor dari jaringan adiposa putih karena adanya stimuli. Adiposit krem sama seperti adiposit cokelat dilengkapi dengan mitokondria yang mengandung uncoupling protein 1 (UCP1), yang ketika teraktivasi akan mengendalikan sintesis ATP dan menstimulasi aktivitas rantai respirasi. Beberapa regulator seperti PPAR γ, PGC-1α, dan PRDM16 muncul sebagai pelaku utama dalam proses diferensiasi adiposit krem.

Tecido adiposo marrom em adultos como alvo de estudo no desenvolvimento de novas terapias para o manejo e tratamento da obesidade: uma revisão integrativa

Introdução: O tecido adiposo marrom foi inicialmente evidenciado em animais e posteriormente em humanos tendo sua função principal a termorregulação. A partir disso, pesquisam-se possibilidades desse tecido auxiliar no controle de massa corporal, a fim de alcançar novas perspectivas no tratamento da obesidade, uma pandemia da atualidade. Objetivo: Compreender o tecido adiposo marrom e abordar hipóteses que caracterizam a contribuição deste no tratamento da obesidade e de suas comorbidades. Materiais e Métodos: Realizou-se uma revisão integrativa na qual foram usados os descritores brown adipose tissue, obesity, thermogenesis, uncoupling protein 1, UCP nas bases de dados PubMed® e Google Acadêmico. Ao todo, 19 artigos e 4 livros referentes às ciências Histologia, Biologia Celular e Fisiologia embasam a revisão. Discussão: O tecido adiposo está presente por todo corpo humano e ocasiona efeitos significantes na fisiologia e patologia do organismo. Os adipócitos que o compõem apresentam diferenças histológicas, biocelulares e de distribuição e subdividem-se em uniloculares e multiloculares. As células multiloculares formam a gordura marrom que é capaz de regular o gasto energético por meio da termogênese adaptativa via proteína desacopladora (UCP). Com esses conhecimentos, buscam-se relações entre o tecido adiposo composto pelas células unicelulares, o qual é o responsável pelo desenvolvimento da obesidade, e o tecido adiposo marrom. Nesse âmbito, dentre as possibilidades de estudo há fatores que influenciam a expressão tecidual da proteína desacopladora e aumentam a termogênese química, há o controle do balanço energético e, ainda, a capacidade de adipócitos marrons de sequestrarem o succinato (flavoproteína que exerce controle agudo sobre a termogênese) da circulação. Conclusão: Foi possível compreender a multifuncionalidade e as características físicas e químicas do tecido adiposo marrom e reconheceu-se esse tecido como um dos potenciais alvos de estudo dada a singularidade epidemiológica da obesidade e seu histórico de tratamentos.

Macrophages expressing uncoupling protein 1 increase in adipose tissue in response to cold in humans

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process.

Mitochondrial H+ Leak and Thermogenesis

Mitochondria of all tissues convert various metabolic substrates into two forms of energy: ATP and heat. Historically, the primary focus of research in mitochondrial bioenergetics was on the mechanisms of ATP production, while mitochondrial thermogenesis received significantly less attention. Nevertheless, mitochondrial heat production is crucial for the maintenance of body temperature, regulation of the pace of metabolism, and prevention of oxidative damage to mitochondria and the cell. In addition, mitochondrial thermogenesis has gained significance as a pharmacological target for treating metabolic disorders. Mitochondria produce heat as the result of H+ leak across their inner membrane. This review provides a critical assessment of the current field of mitochondrial H+ leak and thermogenesis, with a focus on the molecular mechanisms involved in the function and regulation of uncoupling protein 1 and the ADP/ATP carrier, the two proteins that mediate mitochondrial H+ leak. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.