Gastric Bypass in Male Rats Alters Neuroendocrine but not Behavioral Arms of the Stress Axis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 72-87-HPA Axis
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-83
Bernadette Elizabeth Grayson*1, Andrew P Hakala-Finch2, Melani Kekulawala2, Holly Laub2, Anne E Egan2, Stephen C Woods3, James P Herman4, Randy J Seeley4, Stephen C Benoit4 and Yvonne M Ulrich-Lai1
1University of Cincinnati, Cincinnati, OH, 2University of Cincinnati, 3Univ of Cincinnati Med Ctr, Cincinnati, OH, 4Univ of Cincinnati, Cincinnati, OH
Both Metabolic Syndrome (MetS) and stress-related psychiatric disorders (depression, anxiety and addictions) are highly-prevalent in the United States. It has been suggested that weight loss may be an effective strategy to treat not only MetS, but also accompanying stress-related psychiatric disorders. Currently pharmacologic treatments result in small transient reductions in body-weight. Several bariatric surgeries, however, produce sustained body-weight reduction in obese individuals. An important unanswered question is whether surgically-induced weight-loss ameliorates stress-related psychiatric disorders. Thus, the present work addresses the hypothesis that bariatric surgery reduces behavioral and neuroendocrine indices of stress-related psychiatric disorders in rats

We maintained adult Long Evans male rats on either a low-fat chow (10% fat) or a palatable high-fat diet (HFD) (41% butter fat) prior to surgery. Animals received either sham surgery (SHAM), vertical sleeve gastrectomy (VSG) or roux-en-Y gastric bypass (RYGB).  Both VSG and RYGB lost approximately 15% of their body weight following the surgeries. Four weeks after surgery, anxiety- and depressive-like behaviors were assessed in all 4 groups.  Both obese SHAM rats and surgically-induced lean rats (VSG and RYGB) had a minimal phenotype with respect to either anxiety-like (elevated plus maze) or depressive-like (modified forced swim test) stress behaviors. However, RYGB increased basal tone of the HPA axis as measured by a.m. and p.m. corticosterone. RYGB also produced thymic involution and adrenal hyperplasia, consistent with the idea of increased basal HPA drive. Moreover, during an acute novel environment test, RYGB exhibited reduced plasma ACTH and corticosterone responses to the stress, suggestive of reduced post-stress HPA responsivity, possibly due to increased negative feedback from the elevated basal glucocorticoids.

Collectively, these data suggest that while VSG and RYGB result in equivalent improvements in metabolic parameters, these surgeries differentially affect the HPA axis. RYGB exhibit an overall increase in basal (non-stress) HPA axis activity.  Differences between RYGB and VSG may be attributable to the altered milieu of circulating metabolic hormones that have differential patterns and levels of release following these surgeries.

Disclosure: RJS: Board Member, Johnson &Johnson, Investigator, Johnson &Johnson, Consultant, Novo Nordisk, Investigator, Novo Nordisk. SCB: Research Funding, Johnson &Johnson. Nothing to Disclose: BEG, APH, MK, HL, AEE, SCW, JPH, YMU

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Funding: The work of the laboratory is supported in part by NIH Awards DK56863, DK57900, U01CA141464, DK082480, MH069860, DK08248, DK017844 and also from Ethicon Endo-Surgery Inc., F. Hoffman-La Roche Ltd., Pfizer Inc. and Novo Nordisk A/S. BEG is supported by NIH Award 1F32HD68103.