Suppression of food intake, body weight, and body fat by jejunal fatty acid infusions.

Three experiments investigated effects of jejunal lipid infusions given on 4 or 21 consecutive days in adult, male Sprague-Dawley rats. In experiment 1, 7-h infusions of linoleic or oleic acid (0.2 ml/h for 7 h; total load = 11.5 kcal) on 4 consecutive days reduced total intake (ad libitum consumption of the liquid diet Boost, Mead Johnson, plus load) by approximately 15% and decreased weight gain compared with 4-day tests with saline administration. In experiment 2, linoleic acid at 0.1 ml/h for 7 h (5.7 kcal) was ineffective, whereas the same load delivered in 3.5 h produced effects similar in magnitude to those in the first experiment. In experiment 3, jejunal infusions of linoleic acid (0.2 ml/h for 7 h) on 21 consecutive days reduced mean total intake by 16%, body weight by 10%, and carcass fat by 48% compared with controls receiving saline. The net decrease in caloric intake may reflect the combined activation of pre- and postabsorptive mechanisms, and it suggests a possible treatment for obesity.

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat.

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in approximately 50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.

Induction and relief of nasal congestion in ferrets infected with influenza virus.

Susceptible ferrets intranasally infected with influenza virus consistently responded with maximal nasal secretion of virus, febrile reaction, and influx of inflammatory cells into nasal lumen on day 2 post infection (d.p.i.). Polymorphonuclear leucocytes were the earliest predominant cell, followed by monocytes/macrophages while lymphocytes were maintained as a minor population throughout the 7-day period. Nasal congestion level, continuously monitored by computer aided active anterior rhinomanometry, was reproducibly maximal at 2 d.p.i., diminished in intensity the next day and returned to the basal level within 7 d.p.i. Nasal congestion was effectively relieved by a single intranasal dose of 0.1% oxymetazoline or 0.2% phenylephrine, or a single intragastric administration of pseudoephedrine. Intranasal delivery of a single dose of 1% pyrilamine relieved nasal congestion while 0.8% ipratropium bromide and 30% cimetidine were ineffective. These results suggested that nasal congestion is regulated by alpha-adrenergic receptors in the mucosal vasculature or by H1 histamine receptor, but is unaffected by inhibitors of nasal secretion regulated by the cholinergic nervous system. The present study indicates that the infectious rhinitis ferret model provides a reproducible nasal congestion pattern that can be objectively measured by a refined active anterior rhinomanometric system. This labour intensive measurement, however, makes it difficult either to conduct a large population animal study or to use it for a rapid throughput screening of new drugs. The temporal relation between the influx of inflammatory cells into the nasal lumen and the onset of nasal congestion underlies the model's relevance to the exploration of the pathogenic mechanism(s) during viral rhinitis.