Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet

Abstract

Depression and altered serum lipids in cynomolgus monkeys on a Western diet. Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a ‘Western’ diet, enriched with saturated fat and cholesterol. Socially-housed adult female cynomolgus monkeys (n=36) were fed the Western diet for 27 months and depressive behavior was recorded weekly. Body weight, body mass index and circulating cholesterol profiles were measured in all animals, and fatty acids (FA) and FA-based signaling molecules were measured in the 6 least and 6 most depressed monkeys. Monkeys consuming the Western diet exhibited a broad range of percent time spent in depressive behavior. The percent time spent depressed was positively correlated with total plasma and LDL cholesterol and negatively correlated with HDL cholesterol. Despite being leaner, depressed monkeys had higher concentrations of monounsaturated fats (C16:1 and C17:1), a higher ω6/ω3 polyunsaturated fatty acid (PUFA) ratio and higher concentrations of omega-6 (ω6) PUFAs, particularly C18:2ω6 and C20:3ω6. FA ratios suggest that stearoyl CoA desaturase 1 activity was increased in depressed monkeys. Depressed female cynomolgus monkeys had elevated concentrations of serum lipids and lipid signaling molecules that are typically associated with obesity, insulin resistance and cardiovascular disease, which may account in part for the comorbidity of depression and CHD.

The impact of treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease, behavior, and neuroanatomy

“…For this reason we examined coronary artery atherosclerosis extent in monkeys that had, or had not exhibited depressive behavior in the previous 4 years. We found that depressed monkeys had four times the atherosclerosis in their coronary arteries as their nondepressed counterparts (Shively et al, 2009; Shively et al, 2008; Chilton et al, 2011). …”

High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets

“…Careful parsing of behavior data indicated that HFD markedly decreased attention to testing (Reyes, 2014). HFD precipitates depressive behaviors in macaques, (Chilton et al, 2011, Shively et al, 2008), and cognitive impairment in rodents (Pistell et al, 2010, White et al, 2009). …”

Behavioral and neurobiological characteristics of social stress versus depression in nonhuman primates

“…Dom: dominant animals; Sub: subordinate animals; R: response; Dex: dexamethasone; ACTH: adrenocorticotropin hormone; CRH: corticotrophin-releasing hormone; P4: progesterone; ovx: ovariectomized; CSF: cerebrospinal fluid; HVA: homovanillic acid; 5-HT 1A : Serotonin 1A receptor; BP: binding potential; D2: dopamine receptor D2; TPC: total plasma cholesterol; HDL-C: high density lipoprotein cholesterol. Sources: Chilton et al, 2011; Grant et al, 1998; Hamm et al, 1983; Kaplan et al, 2002; Kaplan et al, 2009; Morgan et al, 2000; Riddick et al, 2009; Shively and Clarkson, 1994; Shively et al, 1995; Shively et al, 2003; Shively et al, 2006; Willard et al, 2009; Willard et al, 2011. …”