Blunted Re-Feeding Response and Increased Locomotor Activity in Mice Lacking FoxO1 in Synapsin-Cre-Expressing Neurons.

Blunted Re-feeding Response And Increased Locomotor Activity In Mice Lacking FoxO1 In Synapsin-Cre-Expressing Neurons.

Diabetes. 2013 Jul 8;
Ren H, Plum-Morschel L, Gutierrez-Juarez R, Lu TY, Kim-Muller JY, Heinrich G, Wardlaw SL, Silver R, Accili D

Successful development of anti-obesity agents requires detailed knowledge of neural pathways controlling body weight, eating behavior, and peripheral metabolism. Genetic ablation of FoxO1 in selected hypothalamic neurons decreases food intake, increases energy expenditure, and improves glucose homeostasis, highlighting this gene’s role in insulin and leptin signaling. But little is known about potential effects of FoxO1 in other neurons. To address this question, we executed a broad-based neuronal ablation of FoxO1 using Synapsin promoter-driven Cre to delete floxed Foxo1 alleles. Lineage-tracing experiments showed that NPY/AgRP and POMC neurons were minimally affected by the knockout. Nonetheless, Syn-Cre-Foxo1 knockouts demonstrated a catabolic energy homeostatic phenotype, with a blunted refeeding response, increased sensitivity to leptin and amino acid signaling, and increased locomotor activity, likely due to increased melanocortinergic tone. We confirmed these data in mice lacking the three Foxo genes. The effects on locomotor activity could be reversed by direct delivery of constitutively active FoxO1 to the mediobasal hypothalamus, but not to the suprachiasmatic nucleus. The data reveal that the integrative function of FoxO1 extends beyond the arcuate nucleus, suggesting that CNS inhibition of FoxO1 function can be leveraged to promote hormone sensitivity and prevent a positive energy balance. HubMed – eating

Antipsychotic-Induced Insulin Resistance and Postprandial Hormonal Dysregulation Independent of Weight Gain or Psychiatric Disease.

Diabetes. 2013 Jul 8;
Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen HL, Rickels K

Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior. HubMed – eating

Food Purchasing Sites: Repercussions For Healthy Eating.

Appetite. 2013 Jul 5;
Costa JC, Claro RM, Martins AP, Levy RB

Changes in the food system are associated with the increase in consumption of foods with low nutritional value in recent decades. Data on food purchasing for household consumption, collected from the Instituto Brasileiro de Geografia e Estatística (IBGE – Brazilian Institute of Geography and Statistics) Household Budget Survey (HBS) in 2002-3, were used to describe the contribution of food purchasing sites (FPS) to the diet of Brazilian families. All the 241 distinct FPS mentioned in the HBS were grouped into ten categories, according to the nature of the products available. Food acquisitions were organized into seven groups. Supermarkets and hypermarkets accounted for 49% of the acquisitions and were the main source of six out of the seven food groups. Street markets and greengroceries stood out in the acquisitions of fruits and vegetables, accounting for 39% of this market. The large contribution of supermarkets and hypermarkets to the diet shows the need for healthy eating promotion policies aiming at these locations. Street markets and greengroceries represent important allies for healthy eating. HubMed – eating