Impaired brown adipose tissue is differentially modulated in insulin-resistant obese wistar and type 2 diabetic Goto-Kakizaki rats

Serdan, Tamires Duarte Afonso; Masi, Laureane Nunes; Pereira, Joice Naiara Bertaglia; Rodrigues, Luiz Eduardo; Alecrim, Amanda Lins; Scervino, Maria V. M.; Diniz, Vinícius Leonardo Sousa; Santos, Alef Aragão Carneiro dos; Sousa-Filho, Celso Pereira Batista; Alba-Loureiro, Tatiana Carolina; Marzuca‐Nassr, Gabriel Nasri; Bazotte, Roberto Barbosa; Gorjão, Renata; Pithon-Curi, Tânia Cristina; Curi, Rui; Hirabara, Sandro Massao

doi:10.1016/j.biopha.2021.112019

Cited by 9 publications

(12 citation statements)

References 87 publications

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Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

“…In a non-obese model of T2D, which shares a susceptibility locus on chromosome 10 like in humans, lower cell density and higher adipocyte area were recorded in Goto-Kakizaki rats ( 120 ). Interestingly, glucose uptake in BAT was impaired in both baseline and even after 30 min of stimulation with 1 mg/kg CL316,243, a β3-adrenergic agonist ( 120 ). Subsequently, there was an increased expression of genes involved in fatty acid oxidation (CPT1 and CPT2), BAT metabolism (Sirt1 and PGC1α), but decreased gene expression of GLUT-1 compared to other experimental groups ( 120 ).…”

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

“…In the same study, they demonstrated that counteracting BAT whitening using PPARα agonists can help to ameliorate the complications associated with obesity ( 119 ). The combination of HFD and high-sugar diet impaired BAT function in Wistar rats ( 120 ). The evidence of whitening in these animals was marked by the increased adipocytes area and decreased expression of BAT markers, such as FGF21, PPARγ, SIRT1, and CPT1, as well as the genes involved in the insulin signaling including insulin receptor substrate 2 (IRS-2), and glucose transporter (GLUT)-4 ( 120 ).…”

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

“…Interestingly, glucose uptake in BAT was impaired in both baseline and even after 30 min of stimulation with 1 mg/kg CL316,243, a β3-adrenergic agonist ( 120 ). Subsequently, there was an increased expression of genes involved in fatty acid oxidation (CPT1 and CPT2), BAT metabolism (Sirt1 and PGC1α), but decreased gene expression of GLUT-1 compared to other experimental groups ( 120 ). Possibly, impairment of the β3-adrenergic response could suggest an increased expression of the above-mentioned genes, acting as a compensatory mechanism.…”

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

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An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

et al. 2023

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Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as a potential avenue to combat obesity. Although BAT is the opposite of white adipose tissue (WAT) which is responsible for energy storage, BAT shares thermogenic capacity with beige adipose tissue that emerges from WAT depots. This is unsurprising as both BAT and beige adipose tissue display a huge difference from WAT in terms of their secretory profile and physiological role. In obesity, the content of BAT and beige adipose tissue declines as these tissues acquire the WAT characteristics via the process called “whitening”. This process has been rarely explored for its implication in obesity, whether it contributes to or exacerbates obesity. Emerging research has demonstrated that BAT/beige adipose tissue whitening is a sophisticated metabolic complication of obesity that is linked to multiple factors. The current review provides clarification on the influence of various factors such as diet, age, genetics, thermoneutrality, and chemical exposure on BAT/beige adipose tissue whitening. Moreover, the defects and mechanisms that underpin the whitening are described. Notably, the BAT/beige adipose tissue whitening can be marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation.

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Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

Section: Factors Inducing Bat/beige Adipose Tissue Whitening or Inact...mentioning

confidence: 99%

See 2 more Smart Citations

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

et al. 2023

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“…The authors reported a process of whitening and impaired function in the BAT of 16-week-old GK rats, decreased gene expression of glucose transporter 1, and an increase in expression of genes involved in fatty acid oxidation, BAT metabolism, and leptin serum concentrations. A histological evaluation of BAT indicated reduced cellular density with greater adipocyte area in GK rats ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

Gimenes

Santana

Scervino

et al. 2022

Braz J Med Biol Res

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The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

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Insulin resistance in nonobese type 2 diabetic Goto Kakizaki rats is associated with a proinflammatory T lymphocyte profile

Lobato,

Manoel,

Pereira

et al. 2024

FEBS Letters

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Goto‐Kakizaki (GK) rats develop a well‐defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T‐regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata‐3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti‐inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.

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Impaired brown adipose tissue is differentially modulated in insulin-resistant obese wistar and type 2 diabetic Goto-Kakizaki rats

Cited by 9 publications

References 87 publications

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

Insulin resistance in nonobese type 2 diabetic Goto Kakizaki rats is associated with a proinflammatory T lymphocyte profile

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