Plant Extracts in Obesity: A Role of Gut Microbiota

Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota.

Novel Insights Into Monogenic Obesity Syndrome Due to INPP5E Gene Variant: A Case Report of a Female Patient

A Caucasian girl with consanguineous parents presented with early severe obesity and retinal dystrophy. A novel, homozygous gene truncating variant (c.1897C>T) in the INPP5E gene confirmed the diagnosis of MORMS (OMIM #610156). A novel clinical finding in the presented syndrome is progressive cone-rod type retinal dystrophy diagnosed at the age of four months that progressed in the 1st decade of life. Severe obesity, insulin resistance with hyperinsulinism, and impaired glucose tolerance developed alongside other components of the metabolic syndrome - dyslipidemia, arterial hypertension, and obstructive hypopnea in sleep. At the age of 14 years, primary amenorrhea persists. The patient is managed by regular nutritional advice, metformin, antihypertensive medication, and non-invasive respiratory support during sleep. Differential diagnosis of this rare entity is discussed in extend.

RNA sequencing and microarray analysis are helpful techniques to detect obesity-related lncRNAs. LncRNA can alter cholesterol metabolism and can be a target for gene therapy

Recent study has connected obesity disorders including improper lipid, cholesterol, and glucose metabolism to lncRNAs, which may lead to obesity or type 2 diabetes. RNA sequencing and microarray analysis are helpful techniques to detect obesity-related lncRNAs. However, the important participation of several lncRNAs in controlling obesity problems is yet unexplored.Several lncRNAs interact with and influence lipid, cholesterol, and glucose metabolism genes, proteins, and enzymes. However, the number of lncRNAs found is substantially smaller than the number of lncRNAs detailing the lipid, cholesterol, and glucose metabolic activity. This is due in part to the complexity of the action mechanism of lncRNAs and the lack of reliable methodologies to predict functional properties of lncRNA. Consequently, if technologies exist to uncover and define lncRNAs connected to obesity syndrome, it will disclose possible therapeutic goals and drive the creation of novel, very useful ways for obesity therapy. Moreover, lncRNA can alter cholesterol accumulation, synthesis, intracellular transit, and excretion. Whether lncRNAs impact cholesterol homeostasis through cholesterol esterification, deesterification, and/or absorption remained unresolved till recently. It's worth highlighting that lncRNAs have poor species conservation levels. According to a recent study, about 10% of lncRNAs are preserved between mammals and chickens and 2% between mammals and fish,106 showing that preserved lncRNAs between species may play a crucial role in modulating the metabolism of obesity in animal evolution. Despite their poor conservation between species, however, most nonconservative lncRNAs have the potential to be transformed into nucleic acid medications to treat obesity syndrome in animal studies or for therapeutic advantages.LncRNAs play a function in food intake, associated with obesity diseases. LncRNA was revealed to have a role in HFD-induced obesity diseases, which have intergenerational characteristics. Complete decipherment of lncRNA with regard to metabolic control of obesity might open the way for precise medication and prevention of obesity transmission from generation to generation. Moreover, as indicated in this study review, lncRNA-based therapeutic approaches may minimize genetic toxicity and maybe treat obesity problems. Natural products may have a lot of promise in the treatment of obesity syndrome and additional studies are needed. Future investigation may focus on finding effective and nontoxic strategies to introduce lncRNA interference agents to obese patients via natural products and gene therapy. As a consequence, discovering a unique mechanism for influencing obesity on the expression of lncRNA might help us better understand the pathophysiology of obesity syndromes and support the design of new tools to prevent and cure obesity syndrome, especially from food.

MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice

Melanin-concentrating hormone (MCH) is a 19 amino acid long peptide found in the brain of animals, including fishes, batrachians, and mammals. MCH is implicated in appetite and/or energy homeostasis. Antagonists at its receptor (MCH-R1) could be major tools (or ultimately drugs) to understand the mechanism of MCH action and to fight the obesity syndrome that is a worldwide societal health problem. Ever since the deorphanisation of the MCH receptor, we cloned, expressed, and characterized the receptor MCH-R1 and started a vast medicinal chemistry program aiming at the discovery of such usable compounds. In the present final work, we describe GPS18169, a pseudopeptide antagonist at the MCH-R1 receptor with an affinity in the nanomolar range and a Ki for its antagonistic effect in the 20 picomolar range. Its metabolic stability is rather ameliorated compared to its initial parent compound, the antagonist S38151. We tested it in an in vivo experiment using high diet mice. GPS18169 was found to be active in limiting the accumulation of adipose tissues and, correlatively, we observed a normalization of the insulin level in the treated animals, while no change in food or water consumption was observed.