Obesity Triggers Dysregulation of Essential ABC Transporters in Rat Testis and Sperm

Péter Szatmári1, Kata Kira Kemény1, Adrienn Seres-Bokor1

  • 1Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös Street 6, 6720 Szeged, Hungary.

Nutrients
|June 12, 2026
PubMed

Insights

Diet-induced obesity alters ABC transporters in male rats, impacting fertility. These changes in P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) occur even without affecting testosterone levels.

Area of Science:

  • Reproductive Biology
  • Metabolic Dysfunction
  • Molecular Biology

Background:

  • Obesity and metabolic dysfunction negatively impact male fertility at a molecular level.
  • ABC transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are implicated in testicular and sperm function.
  • Diet-induced obesity models are crucial for understanding metabolic impacts on reproductive health.

Purpose of the Study:

  • To investigate the effects of short-term diet-induced obesity on testicular and spermatic ABC transporter expression (P-gp/Abcb1 and BCRP/Abcg2) in a rat model.
  • To evaluate the impact of obesity on the testicular androgen state, including aromatase (Cyp19a1), androgen receptor (Ar), and testosterone levels.

Main Methods:

  • Male Sprague Dawley rats were fed a high-fat, high-sugar diet (HFHSD) for 10 weeks to induce obesity.
  • Metabolic status was assessed via glucose tolerance tests; reproductive organ weights were measured.
  • Gene and protein expression of Abcb1a/1b, Abcg2, Cyp19a1, and Ar in testes and sperm were analyzed using RT-PCR and Western blotting; testosterone levels were measured by ELISA.

Main Results:

  • Obesity induction led to increased weight gain, glucose intolerance, and reduced reproductive organ size.
  • Testicular P-gp (Abcb1a/1b) expression increased, while BCRP (Abcg2) expression decreased in obese rats.
  • Spermatic expression of Abcb1a/1b and Abcg2 mRNA was reduced in obese rats; no significant changes were observed in testicular testosterone, Cyp19a1, or Ar mRNA levels.

Conclusions:

  • Diet-induced obesity causes significant alterations in key ABC transporters within the testes and sperm of male rats.
  • These ABC transporter changes may contribute to fertility impairments in obese males, independent of androgen dysregulation.
  • The findings highlight ABC transporters as potential early molecular indicators of obesity-related male infertility.

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Pharmacokinetics in Obese Patients: Drug Absorption and Distribution01:25

Pharmacokinetics in Obese Patients: Drug Absorption and Distribution

Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
Drug Dosing: Obese Patients01:21

Drug Dosing: Obese Patients

In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
Obesity01:24

Obesity

The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in adipocytes...
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...