The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

Previous research has shown that the brain is an important target of diabetic complications. Since brain regions are interconnected to form a large-scale neural network, we investigated whether severe hyperglycemia affects the topology of the brain network in people with type 2 diabetes. Twenty middle-aged (average age: 54 years) individuals with poorly controlled diabetes (HbA1c: 8.9−14.6%, 74−136 mmol/mol) and 20 age-, sex-, and education-matched healthy volunteers were recruited. Graph theoretic network analysis was performed with axonal fiber tractography and tract-based spatial statistics (TBSS) using diffusion tensor imaging. Associations between the blood glucose level and white matter network characteristics were investigated. Individuals with diabetes had lower white matter network efficiency (P<0.001) and longer white matter path length (P<0.05) compared to healthy individuals. Higher HbA1c was associated with lower network efficiency (r = −0.53, P = 0.001) and longer network path length (r = 0.40, P<0.05). A disruption in local microstructural integrity was found in the multiple white matter regions and associated with higher HbA1c and fasting plasma glucose levels (corrected P<0.05). Poorer glycemic control is associated with lower efficiency and longer connection paths of the global brain network in individuals with diabetes. Chronic hyperglycemia in people with diabetes may disrupt the brain’s topological integration, and lead to mental slowing and cognitive impairment.

Pituitary GH1 is essential for postnatal growth and regulation of metabolism of fat, carbohydrate, and protein in animals. At the tissue level these pleiotropic actions of GH result from the interaction of GH with the GH receptor. Hence, regulating the expression of and modulating the function of the GH receptor is critical for the action of GH in the intact animal. The promoter-regulatory regions of the murine (1-4), ovine (5, 6), bovine (7), and human (8) GH receptor genes have been partially characterized. A feature that is common to the GH receptor transcripts from these different species is the heterogeneity in the 5Ј-untranslated region (9). This heterogeneity in the 5Ј-UTR results from splicing of the various exon 1 fragments to a common splice site located 11 bp upstream of the initiating ATG. Whereas the number of 5Ј-untranslated exons varies among species, in all examples the location of the splice site from the initiating ATG is constant. In the human liver there are at least eight distinct 5Ј-UTRs (V1-V8), with the most common GH receptor variant being termed V1 (9). The identity and distribution of the 5Ј-untranslated exons in other tissues of the body, in which significant expression of GH receptor occurs and which are targets of GH action, such as kidney and heart, are as yet unknown. In the rat five distinct 5Ј-UTRs (GHR 1-5 ) have been identified (10, 11). The class of RNA containing the GHR 1 5Ј-UTR variant is expressed only in liver, is far more abundant in females than in males, and is specifically increased during pregnancy (11). In the sheep two 5Ј-UTRs have been described (5, 6). Exon 1A is a liver-specific transcript and is homologous to the human V1 transcript. Another UTR termed exon 1B displays a striking GC content of 79% and is homologous to the human V2, rat GHR2, and mouse L2. In the cow three 5Ј-UTRs, termed 1A, 1B, and 1C, have been identified (7).In the mouse two 5Ј-UTRs, termed L1 and L2, have been characterized (4). Expression of the L1 and L2 transcripts is regulated in a tissue-and development stage-specific manner. The L1-GH receptor transcript is expressed in liver only during pregnancy (3,12). Late pregnant mouse liver and placenta both express GHR mRNAs containing L1 and L2 sequences (12). In the placenta L2-GHR UTRs are more abundant than L1-GHR UTRs. Information regarding the specific factors regulating expression of the different UTRs is at present limited to that for the mouse L1 UTR. All identified proximal and distal regulatory elements contain a core CCAAT sequence (4). An enhancer element located approximately 3 kb upstream from the transcription start site of the L1 transcript interacts with the transcription factor CTF/NF-1 in COS-7 cells (2). The most distal cis-element identified to date in the mouse promoter is located 3.6 kb 5Ј to the transcription start site, and two CCAAT boxbinding proteins, MSY-1 and NF-Y, regulate the activity of the L1 promoter via interaction with this cis-element (3). Furthermore, the intracellular distribution of the MSY-1 protein ...