Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion

Hypothalamic anorexigenic [corticotropin-releasing factor (CRF) and proopiomelanocortin] peptides decrease and the orexigen, neuropeptide Y, increases with diabetic hyperphagia. However, when diabetic rats are allowed to eat lard (saturated fat) as well as chow, both caloric intake and hypothalamic peptides normalize. These neuropeptide responses to lard require an intact hepatic vagus [la Fleur et al. (2003) Diabetes, 52, 2321-2330]. Here, we delineate temporal interactions after lard consumption +/- hepatic vagotomy (HV) between feeding and brain neuropeptide expression in insulin-dependent diabetic rats. CRF-mRNA was reduced in the paraventricular nuclei (PVN) by 6 h after presentation of lard, before caloric intake increased in HV-diabetic rats, and did not increase at 30 or 36 h, as it did in shamHV-diabetic rats eating lard. CRF-mRNA was increased in the bed nuclei of the stria terminalis of HV-diabetic rats compared with shamHV-diabetic rats only when caloric intake was high at 30 or 36 h. At 36 h, shamHV-diabetic rats eating chow had increased CRF-mRNA in the central amygdala but diabetic rats eating lard had decreased CRF-mRNA, whereas HV-diabetic rats eating chow or lard had normal CRF-mRNA in the central amygdala. We conclude that eating lard restores peptide expression to normal in the hypothalamus of diabetic rats, and because decreased CRF-mRNA in the PVN precedes the increase in caloric intake in HV-diabetic rats eating lard, that the loss of a hepatic vagal signal to PVN may be responsible for increased intake; moreover, CRF-mRNA in limbic structures is also sensitive to both HV and lard ingestion in diabetic rats.