Fasting-induced activity changes in MC3R neurons of the paraventricular nucleus of the thalamus.

The brain controls energy homeostasis by regulating food intake through signaling within the melanocortin system. Whilst we understand the role of the hypothalamus within this system, how extra-hypothalamic brain regions are involved in controlling energy balance remains unclear. Here we show that the melanocortin 3 receptor (MC3R) is expressed in the paraventricular nucleus of the thalamus (PVT).

Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice.

Objective: The incidence of gestational diabetes mellitus (GDM) and metabolic disorders during pregnancy are increasing globally. This has resulted in increased use of therapeutic interventions such as metformin to aid in glycemic control during pregnancy. Even though metformin can cross the placental barrier, its impact on offspring brain development remains poorly understood.

Gut-derived peptide hormone receptor expression in the developing mouse hypothalamus.

Objective: In adult organisms, a number of receptors have been identified which modulate metabolic processes related to peptides derived from the intestinal tract. These receptors play significant roles in glucose homeostasis, food intake and energy balance. Here we assess these classical metabolic receptors and their expression as well as their potential role in early development of hypothalamic neuronal circuits.

Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior.

Growth differentiation factor 15 (GDF15) is a mitochondrial stress-induced cytokine that modulates energy balance in an endocrine manner. However, the importance of its brainstem-restricted receptor GDNF family receptor alpha-like (GFRAL) to mediate endocrine GDF15 signaling to the brain upon mitochondrial dysfunction is still unknown. Using a mouse model with muscle-specific mitochondrial dysfunction, we here show that GFRAL is required for activation of systemic energy metabolism via daytime-restricted anorexia but not responsible for muscle wasting.

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction.

Diabetes, obesity, and Alzheimer's disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein-cleaving (APP-cleaving) enzyme 1 (BACE1), APP, and β-amyloid (Aβ) are linked with vascular disease development and increased BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, increased Aβ, and vascular dysfunction is unclear.