Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking, and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress-coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seeking, and altered stress response) in obese animals.

Ambulatory care increased vitamin B12 requirement associated with chronic acid suppression therapy.

BACKGROUND: Assimilation of vitamin B(12) from dietary sources requires gastric acid. By decreasing acid production, the proton pump inhibitors (PPIs) and histamine(2) (H(2))-blockers may reduce vitamin B(12) absorption. OBJECTIVE: To determine whether chronic acid suppression therapy is associated with the initiation of vitamin B(12) supplementation, we conducted a retrospective case-control study using a state-wide Medicaid population. METHODS: Case patients were identified as those who initiated vitamin B(12) supplementation during the study period. Four control patients were age- and gender-matched to each case. Patients (n = 109 844) with a paid claim between September 27, 1995, and September 27, 1997, were eligible for inclusion. Chronic acid suppression therapy was defined as treatment with H(2)-blockers or PPIs for >/=10 of the 12 months prior to the first vitamin B(12) injection. Comparisons were made between the case and control groups regarding exposure to chronic acid suppression therapy. RESULTS: One hundred twenty-five cases were matched to 500 controls. Twenty-three patients (18.4%) had been exposed to chronic acid suppression therapy compared with 55 (11.0%) of the control group (p = 0.025; OR 1.82; 95% CI 1.08 to 3.09). CONCLUSIONS: Initiation of vitamin B(12) supplementation was associated with chronic gastric acid suppression therapy.