Down‐regulation of miRNAs in the brain and development of diet‐induced obesity

Abstract

Novel therapeutic interventions for obesity and comorbid conditions require knowledge of the molecular elements playing a role in the development of obesity. Chronic low-grade inflammation has been consistently reported in obese individuals. In this study, we first determined whether key molecular modulators of inflammation, microRNA-155 (miR-155) and microRNA-146a (miR-146a), are regulated by an obesogenic diet within brain regions associated with reward, metabolism and energy balance. C57BL/6J mice were chronically exposed to a high-fat diet (HFD) or a standard chow (CTL). Significant reductions in the levels of miR-155 (82%) and miR-146a (41%) levels were observed within the nucleus accumbens of HFD mice compared to CTL. Further analysis of miR-155 regulation showed no significant changes in levels across peripheral tissue (white adipose, spleen, kidney or liver) between HFD and CTL mice. The effect of lower miR-155 on the development of obesity was determined by exposing wild-type (WT) and miR-155 knockout mice (miR-155 KO) to HFD. Male miR-155 KO gained significantly more weight than WT littermates. Metabolic analyses revealed that miR-155 KO significantly ate more HFD compared to WT, without differing in other metabolic measures including energy expenditure. Together, these data show that miR-155 is physiologically down-regulated after intake of an obesogenic diet, and that loss of miR-155 increases intake of an obesogenic diet. Moreover, these findings shed light on a potential miRNA-based mechanism contributing to the development of diet-induced obesity.

Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis

“…These observations indicate that miRNAs other than miR-103/107 might be involved in the central regulation of body weight and adiposity. For example, miR-155 has recently been suggested to play a role in the central regulation of body weight and food intake ( Maldonado-Avilés et al, 2018 ). In any events, by combining the use of miRNA manipulation with cell lineage, and physiological experiments, the present study reveals a novel role for miR-103/107 in determining the ultimate peptidergic phenotype of hypothalamic neurons involved in glucose regulation.…”

Central Dicer-miR-103/107 Controls Developmental Switch of POMC Progenitors into NPY Neurons and Impacts Glucose Homeostasis

“…These observations indicate that miRNAs other than miR-103/107 might be involved in the central regulation of body weight and adiposity. For example, miR-155 has recently been suggested to play a role in the central regulation of body weight and food intake (Maldonado-Aviles et al, 2018). In any events, by combining the use of miRNA manipulation with cell lineage, and physiological experiments, the present study reveals a novel role for miR-103/107 in determining the ultimate peptidergic phenotype of hypothalamic neurons involved in glucose regulation.…”

An epigenetic, transgenerational model of increased mental health disorders in children, adolescents and young adults

“…These new set points and relative sensitization of specific brain circuits could contribute epigenetically to increased risk for MHD. In rodent models of stress, obesogenic diet, and substance misuse (methamphetamine, cocaine, and opioids), miRNA levels have been shown to be dynamically regulated in the ventral basal ganglia, and in the methamphetamine model, corresponded to specific shared miRNA levels in circulating serum exosomes [64][65][66][67][68].…”