ArticleNutrition & diabetes2019
Responsiveness of hypothalamo-pituitary-adrenal axis to leptin is impaired in diet-induced obese rats.
Article in Nutrition & diabetes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Seasonal metabolic oscillation: adiposity cycling as a candidate amplifier of mood seasonality in seasonal affective and bipolar disorders.Frontiers in psychiatry · 2026Article
- From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats.ACS chemical neuroscience · 2024Article
- The adipose tissue keeps the score: priming of the adrenal-adipose tissue axis by early life stress predisposes women to obesity and cardiometabolic risk.Frontiers in endocrinology · 2024Review
- Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.Journal of the Endocrine Society · 2023Article
- Dietary Fat Modulation of Gut Microbiota and Impact on Regulatory Pathways Controlling Food Intake.Nutrients · 2023Review
- Adipose tissue, systematic inflammation, and neurodegenerative diseases.Neural regeneration research · 2023Review
- Article
- Metformin effectively restores the HPA axis function in diet-induced obese rats.International journal of obesity (2005) · 2021Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND/
objectivesDiet-induced obese (DIO) rats have altered stress (HPA) axis activity compared to diet-resistant (DR) rats when chronically exposed to a high-fat (HF) diet. Since stress axis is tightly regulated by leptin, an adipocyte-secreted hormone that is important for controlling body weight, we hypothesized that leptin action is impaired in DIO rats leading to alterations in HPA axis activity. SUBJECTS/
methodsWe intraperitoneally injected selectively bred DIO and DR rats with either saline or recombinant rat leptin. HPA axis activity was assessed by measuring norepinephrine (NE) in the paraventricular nucleus (PVN), corticotropin-releasing hormone (CRH) in the median eminence, and serum corticosterone (CORT). To test if HF exposure duration and the corresponding increase in leptin differentially affects HPA axis activity, we placed animals on a chow or HF diet for 1 or 6 weeks.
resultsLeptin injection significantly increased serum leptin levels in both DIO and DR animals. It also reduced PVN NE in both groups, indicating that noradrenergic neurons in both groups remain responsive to leptin. HF diet duration-dependently increased serum leptin only in DIO animals whereas PVN NE increased in both groups. While DR rats responded to HF diet by increasing CRH and CORT at both time-points, responses in DIO rats varied, suggesting that they have altered HPA axis activity that may be dependent on HF-induced leptin levels and/or signaling. To understand the underlying mechanisms, we measured pSTAT-3, a marker of leptin signaling, in brainstem noradrenergic neurons and found reduced pSTAT-3 in A1 region of HF-fed DIO rats. We also found higher serum free fatty acids (FFAs) and a pro-inflammatory cytokine, IL-1β.
conclusionsCollectively, these findings reveal that DIO rats have inherent neuroendocrine impairment in NE-HPA axis circuitry that worsens with the extent of HF diet exposure, possibly due to brainstem leptin resistance and/or elevated circulating FFAs and IL-1β.
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