# Chronic High-Carbohydrate And High-Fat Diet-Induced Metabolic Syndrome Leads To Adrenal Dysfunction, Altered Dendritic Morphology In Limbic Regions, And Anxiety-Like Behaviors In Male Rats

**Authors:** Samuel Treviño, Estefania Fuentes, Berenice Venegas, Guadalupe Muñoz-Arenas, Rubén A. Vázquez-Roque, Fabián Galindo-Ramírez, Everardo Avelino-Cruz, Gonzalo Flores, Jorge Guevara, Alfonso Díaz

PMC · DOI: 10.1007/s12031-026-02501-4 · Journal of Molecular Neuroscience · 2026-03-14

## TL;DR

A high-carb and high-fat diet in male rats causes metabolic syndrome, adrenal issues, brain changes, and anxiety-like behaviors.

## Contribution

This study links long-term high-carb and high-fat diets to limbic dendritic changes and anxiety via HPA axis disruption in rats.

## Key findings

- High-carb and high-fat diets induce metabolic syndrome in male rats.
- Diet-induced metabolic syndrome alters dendritic morphology in limbic brain regions.
- HPA axis dysfunction and increased anxiety-like behaviors are observed in affected rats.

## Abstract

Metabolic syndrome (MS) represents a major global health problem affecting a large proportion of the population. The improper management of peripheral carbohydrates and lipids leads to behavioral changes in neurons of the limbic brain. This work studied male rats that received diets high in carbohydrates, lipids, and their combination for ninety days. The study examined how peripheral metabolic changes and hypothalamic-pituitary-adrenal (HPA) axis alterations affect dendritic structure in limbic brain regions, thereby inducing anxiety-related behavioral responses. Our results show that male rats develop MS after consuming diets high in fat, carbohydrates, and their mixture for an extended period. These diets after the normal function of the HPA axis, leading to increased anxiety symptoms and reduced dendritic growth in limbic areas. This is accompanied by increased caspase-3 immunoreactivity and decreased cell viability. Therefore, it is suggested that diets high in carbohydrates or fats are a critical factor that could induce adrenal stress that damages dendrites and accelerates neurodegeneration, resulting in anxiety-related behavioral changes.

## Linked entities

- **Proteins:** Casp3 (caspase 3)
- **Diseases:** metabolic syndrome (MONDO:0000816)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Ntf3 (neurotrophin 3) [NCBI Gene 81737], Lep (leptin) [NCBI Gene 25608] {aka OB, obese}, Cpox (coproporphyrinogen oxidase) [NCBI Gene 304024], Ca3 (carbonic anhydrase 3) [NCBI Gene 54232] {aka Car3}, Crh (corticotropin releasing hormone) [NCBI Gene 81648] {aka CRF}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}
- **Diseases:** HPA axis dysfunction (MESH:D007027), anxious behavior (MESH:D001523), neuroinflammation (MESH:D000090862), MS (MESH:D024821), brain damage (MESH:D001925), anxiety disorders (MESH:D001008), deficits in (MESH:D009461), hyperglycemia (MESH:D006943), adipocyte hypertrophy (MESH:D006984), adiposity (MESH:D018205), neurodegeneration (MESH:D019636), inflammation (MESH:D007249), Neuronal Hypotrophy (MESH:D009410), compulsive eating (MESH:D000073932), impaired recognition memory (MESH:D008569), Anxiety (MESH:D001007), neurological deterioration (MESH:D009422), hyperplasia (MESH:D006965), weight gain (MESH:D015430), metabolic diseases (MESH:D008659), brain inflammation (MESH:D004660), memory decline (MESH:D060825), Insulin resistance (MESH:D007333), dyslipidemia (MESH:D050171), emotional dysregulation (MESH:D021081), obesity (MESH:D009765), Hypertriglyceridemia (MESH:D015228), Adrenal Dysfunction (MESH:D000307), hyperinsulinemia (MESH:D006946)
- **Chemicals:** AO (MESH:D000165), Carbohydrate (MESH:D002241), DAPI (MESH:C007293), Corticosterone (MESH:D003345), paraformaldehyde (MESH:C003043), sucrose (MESH:D013395), Lipid (MESH:D008055), Glucose (MESH:D005947), Fats (MESH:D005223), water (MESH:D014867), Triglyceride (MESH:D014280), sugar (MESH:D000073893), CD (MESH:D002104), Cholesterol (MESH:D002784), DA (MESH:C025953), paraffin (MESH:D010232), DIFA (-), Fructosamine (MESH:D019270), acridine (MESH:D000166), H (MESH:D006859), Cortisol (MESH:D006854), rhodamine (MESH:D012235), PBS (MESH:D007854), blood glucose (MESH:D001786), TS (MESH:D014316), sodium pentobarbital (MESH:D010424), Triton X-100 (MESH:D017830), ammonium hydroxide (MESH:D064753)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12988920