Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus

Abstract

Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remains highly controversial. Some argue that depression and anxiety lead to increased consumption of "comfort foods," the intake of which reduces negative affect and promotes obesity. In contrast, others have theorized that negative affect results from chronic excessive consumption of highly palatable foods. The brain serotonin (5-HT) system has long been implicated in both the development and treatment of mental illness. Preclinical studies have shown that low brain 5-HT exacerbates depression-and anxiety-like behaviors induced by stress and blocks reductions in depression-like behavior induced by antidepressants, but the effects of brain 5-HT deficiency on responses to high-fat diet (HFD) have not been explored. The current work used genetically modified mice to evaluate the effects of low 5-HT on behavioral and molecular alterations induced by chronic exposure to HFD. Our results reveal that HFD decreases depression-like behavior and increases some anxiety-like behaviors in wild-type (WT) mice. However, genetic brain 5-HT deficiency blocks HFD-induced reductions in forced swim immobility and prevents HFD-induced increases in hippocampal GSK3β phosphorylation despite having no significant effects on HFD-induced changes in body weight or anxiety-like behavior. Together, our results suggest that brain 5-HT deficiency significantly impacts a subset of behavioral and molecular responses to HFD, a finding that could help explain the complex relationships between obesity and mental illness.

Resveratrol‐enhanced SIRT1‐mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors

“…Interestingly, resveratrol successfully abolished the anxiety behaviors at 8 weeks post‐LSI surgery. In past decades, converging evidence indicated that hippocampal inflammation is central to the development of anxiety symptoms in some cases 56‐59 . Clinical evidence reported that patients with anxiety disorder exhibit increased concentration of inflammatory cytokines in hippocampus 56 .…”

Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression

“…VMH is the satiety center in the brain that regulates food intake, glucose and energy metabolism via different downstream targets. A recent research discovers the inhibition of peripheral 5-HT synthesis lead to resistance to HFD-induced obesity and can attenuate HFD-induced depression-like behavior ( 42 ).VMH is an important center that integrate peripheral metabolic signal ( 43 ). Our previous study found that high fat diet-fed mice with impaired glucose tolerance expressed lower level of BDNF mRNA in VMH.…”

Dietary and metabolic risk of neuropsychiatric disorders: insights from animal models

“…However, in Tph2 R439H KI mice with brain 5-HT deficiency, HFD intervention did not significantly affect weight, anxiety-like behaviour or depression-like behaviour. This preliminary study suggests that 5-HT deficiency in the brain has a significant effect on HFD-induced behaviour and the molecular response [94]. Suarez's study [101] used transgenic mice to assess the effects of cannabinoid type 1 receptor (CB1) knockout on behavioural and molecular changes induced by a HFD (60% kcal from fat) after long-term feeding for 26 weeks.…”