Endocrine Abstracts

Obesity and its consequences, such as type-2 diabetes, cardiovascular disease and cancer, are serious health threats. However, despite what the obesity epidemic might suggest, the balance between caloric intake and expenditure is regulated with tremendous precision under most circumstances. Thus, a regulatory system exists, where deviations from the defended body adiposity level trigger signals that can be monitored by specific intracellular metabolic pathways. Such pathways a...

Obesity and its consequent metabolic disorders are severe health problems. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an important hypothalamic integrator of the actions of nutrients and hormones on food intake (FI). Nutrient availability also affects the formation of reactive oxygen species (ROS) in the hypothalamus and regulates neuronal activity. In the present study, we hypothesise that modulation of mTORC1 activity mediates ROS effects on FI. To thi...

It is well known that cannabinoid type 1 receptor (CB1) antagonist drugs may reduce body weight and improve metabolic profiles in obese animals and humans by a double mechanism: at first, targeting mesolimbic and hypothalamic nuclei and, thereafter, peripheral organs involved in energy storage and expenditure. However, it is still unknown which of these sites of action may have a predominant role in the endocannabinoid effect on energy balance regulation. To solve this questio...

The brain is critically involved in the regulation of energy balance and glucose homeostasis. Depending on the levels of energy available in our body, the activity of a group of hypothalamic neurons expressing the neuropeptidergic marker proopiomelanocortin (POMC) changes and it plays a key role in maintaining energy balance. When POMC neuronal activity is altered, this can lead to impaired energy homeostasis and therefore to obesity. However, POMC neurons are highly diverse, ...

The brain plays a crucial role in maintaining the body’s energy needs, a process involving the activity of a group of hypothalamic neurons that express the neuropeptidergic marker pro-opiomelanocortin (POMC). POMC neuronal dysfunction can cause obesity and its associated metabolic sequelae. However, this population of neurons is highly diverse at a molecular and functional level, and whether or not such heterogeneity is implicated in disease establishment or progression h...

Bile acids (BA) are cholesterol-derived molecules that are mostly known for their involvement in lipid digestion and absorption. Recent evidence recognizes them as metabolic integrators able to reduce body weight (BW), increase energy expenditure (EE) and improve glycemic control by activating their specific receptor, the Takeda G protein-coupled receptor 5 (TGR5) in peripheral organs. These outcomes have increased importance in the context of diet-induced obesity and associat...

Type 2 diabetes is among the most prevalent chronic diseases worldwide. Further research is needed to identify new mechanisms that may help preserve the function of insulin-secreting pancreatic β-cells. The cannabinoid receptors type 1 (CB1) and their endogenous ligands, endocannabinoids, exert a key role in regulating of glucose homeostasis, β-cells function, and insulin secretion. Intriguingly, CB1 is not only located at the plasma membrane (pmCB1), but also at the...

Obesity and type–2 diabetes (T2D) represent a global health crisis. However, only a few, and often sub–effective pharmacological tools are available to treat these disorders. Though beneficial for glycemic control, GLP–1 receptor (GLP–1R) agonists show scarce weight–lowering and insulin–sensitizing efficacy.New molecules able to selectively block the activity of the cannabinoid receptor type–1 (CB1R) in periphera...

The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to counteract diet induced obesity (DIO). An unsolved question is whether the effects of CB1 blockade on energy balance are due to peripheral or central mechanisms. This is an important clinical issue since the CB1 antagonist drugs have recently been withdrawn from the market due to their psychiatric side effects, and novel drugs selectively acting at peripheral le...