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Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications.

ABSTRACT: There is a rapidly increasing prevalence of obesity and related metabolic disorders such as type 2 diabetes worldwide. White adipose tissue (WAT) stores excess energy, whereas brown and beige adipose tissues consume energy to generate heat in the process of thermogenesis. Adaptive thermogenesis occurs in response to environmental cues as a means of generating heat by dissipating stored chemical energy. Due to its cumulative nature, very small differences in energy expenditure from adaptive thermogenesis can have a significant impact on systemic metabolism over time. Targeting brown adipose tissue (BAT) activation and converting WAT to beige fat as a method to increase energy expenditure is one of the promising strategies to combat obesity. In this review, we discuss the activation of the thermogenic process in response to physiological conditions. We highlight recent advances in harnessing the therapeutic potential of thermogenic adipocytes by genetic, pharmacological and cell-based approaches in the treatment of obesity and metabolic disorders in mice and the human.

SUBMITTER: Wang CH

PROVIDER: S-EPMC8267903 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications.

Wang Chih-Hao CH Wei Yau-Huei YH

International journal of molecular sciences 20210702 13

There is a rapidly increasing prevalence of obesity and related metabolic disorders such as type 2 diabetes worldwide. White adipose tissue (WAT) stores excess energy, whereas brown and beige adipose tissues consume energy to generate heat in the process of thermogenesis. Adaptive thermogenesis occurs in response to environmental cues as a means of generating heat by dissipating stored chemical energy. Due to its cumulative nature, very small differences in energy expenditure from adaptive therm ...[more]

PMID: 34281227

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Project description:ObjectiveObesity and many of its comorbidities can be improved by nutritional therapy, lifestyle modification, pharmacotherapy, and surgical intervention. Relatively little is known about patients' preferences for the range of obesity treatments. The present study was undertaken to identify factors that may influence these preferences. By evaluating patient-preferred treatment options and factors influencing patients, treatment adherence and efficacy may be improved. Our objective was to identify factors that influence patient preferences and subsequent choice of obesity treatment among those seeking treatment for obesity-related complications.MethodsParticipatory action research, using purposeful sampling, was used to recruit 33 patients with obesity complications. Recruitment took place in specialist clinics for non-alcoholic fatty liver disease, diabetes, hypertension, and chronic kidney disease. Sixteen males and 17 females aged 18-70 years with a BMI>35 kg/m2 were recruited. Prior to the interview, participants watched a 60-min video explaining nutritional therapies, pharmacotherapies, and surgical therapies in equipoise. Data were collected in one-to-one semi-structured interviews using zoom or the telephone; reflective thematic analysis was used.ResultsFour themes emerged: 1) structural factors, 2) autonomy, 3) interaction with formal care, and 4) the emotional and physical consequences of obesity. 39% of participants preferred nutritional therapy with support from medical professionals. 27% chose bariatric surgery. 24% chose pharmacotherapy alone, while 6% chose pharmacotherapy combined with nutritional therapy, 3% of participants wanted no intervention.ConclusionThe challenges can be addressed by increasing support for healthcare professionals toward enhancing both their knowledge and the health literacy of patients. Future research should focus on improving access to treatment pathways for patients as well as developing health literacy programs and educational programs for healthcare professionals.

Project description:Introduction: White adipocytes store lipids, have a large lipid droplet and few mitochondria. Brown and beige adipocytes, which produce heat, are characterized by high expression of uncoupling protein (UCP) 1, multilocular lipid droplets, and large amounts of mitochondria. The rs1421085 T-to-C single-nucleotide polymorphism (SNP) of the human FTO gene interrupts a conserved motif for ARID5B repressor, resulting in adipocyte type shift from beige to white. Methods: We obtained abdominal subcutaneous adipose tissue from donors carrying FTO rs1421085 TT (risk-free) or CC (obesity-risk) genotypes, isolated and differentiated their preadipocytes into beige adipocytes (driven by the PPARγ agonist rosiglitazone for 14 days), and activated them with dibutyryl-cAMP for 4 hours. Then, either the same culture conditions were applied for additional 14 days (active beige adipocytes) or it was replaced by a white differentiation medium (inactive beige adipocytes). White adipocytes were differentiated by their medium for 28 days. Results and Discussion: RNA-sequencing was performed to investigate the gene expression pattern of adipocytes carrying different FTO alleles and found that active beige adipocytes had higher brown adipocyte content and browning capacity compared to white or inactive beige ones when the cells were obtained from risk-free TT but not from obesity-risk CC genotype carriers. Active beige adipocytes carrying FTO CC had lower thermogenic gene (e.g., UCP1, PM20D1, CIDEA) expression and thermogenesis measured by proton leak respiration as compared to TT carriers. In addition, active beige adipocytes with CC alleles exerted lower expression of ASC-1 neutral amino acid transporter (encoded by SLC7A10) and less consumption of Ala, Ser, Cys, and Gly as compared to risk-free carriers. We did not observe any influence of the FTO rs1421085 SNP on white and inactive beige adipocytes highlighting its exclusive and critical effect when adipocytes were activated for thermogenesis.

Dataset Information

Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications.

Publications

Therapeutic Perspectives of Thermogenic Adipocytes in Obesity and Related Complications.

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