Background <p>High-fat diet (HFD) feeding impairs interscapular brown adipose tissue (iBAT) mitochondrial function, leading to lipid accumulation and insulin resistance.</p> Objective <p>To evaluate HFD-induced metabolic impairments in iBAT lipid metabolism using <sup>1</sup>H-MRS and to determine whether chronic cold exposure can restore mitochondrial lipid oxidation.</p> Materials and methods <p>Male Wistar rats (<i>n</i> = 20) were fed either chow diet (CD) or HFD for eight weeks followed by maintained thermoneutral or cold-exposed conditions for two weeks. Lipid content in iBAT was quantified by localized <sup>1</sup>H-MRS on 7 Tesla (Bruker), using 72-mm volume transmit coil and a 2 × 2 phased array receive only cardiac coil and water suppressed PRESS sequence. Systemic insulin sensitivity and mRNA expression of functional genes were quantified to assess thermogenesis, lipolysis, fatty acid oxidation, and mitochondrial functions.</p> Results <p>At thermoneutrality, HFD-fed animals showed increased iBAT lipid fraction (75.3 ± 2% vs. 63.3 ± 1.7%, <i>p</i> &lt; 0.05), elevated plasma glucose and insulin and downregulated UCP1, ATGL, CPT1, and PGC-1α (<i>p</i> &lt; 0.01), indicating impaired oxidative metabolism. Cold exposure significantly reduced iBAT lipid in both CD and HFD groups (<i>p</i> &lt; 0.01) and upregulated functional genes (<i>p</i> &lt; 0.001), restoring mitochondrial functions, lipid oxidation, and thermogenic activity.</p> Conclusion <p>HFD feeding caused insulin resistance and impaired iBAT mitochondrial functions and thermogenic activity, due to lipid accumulation. Chronic cold exposure improved insulin sensitivity and restored iBAT oxidative metabolism and mitochondrial functions.</p>

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Evaluation of high-fat diet-induced metabolic impairments in iBAT lipid metabolism using 1H-MRS

  • Anantharaj Rengaraj,
  • Giang Thi Thu Le,
  • Chandan Dharmashekar,
  • Melvin Khee-Shing Leow,
  • Houchun H. Hu,
  • Chandan Shivamallu,
  • Johan G. Eriksson,
  • S. Sendhil Velan,
  • Balasubramaniem Ashokkumar,
  • Jadegoud Yaligar

摘要

Background

High-fat diet (HFD) feeding impairs interscapular brown adipose tissue (iBAT) mitochondrial function, leading to lipid accumulation and insulin resistance.

Objective

To evaluate HFD-induced metabolic impairments in iBAT lipid metabolism using 1H-MRS and to determine whether chronic cold exposure can restore mitochondrial lipid oxidation.

Materials and methods

Male Wistar rats (n = 20) were fed either chow diet (CD) or HFD for eight weeks followed by maintained thermoneutral or cold-exposed conditions for two weeks. Lipid content in iBAT was quantified by localized 1H-MRS on 7 Tesla (Bruker), using 72-mm volume transmit coil and a 2 × 2 phased array receive only cardiac coil and water suppressed PRESS sequence. Systemic insulin sensitivity and mRNA expression of functional genes were quantified to assess thermogenesis, lipolysis, fatty acid oxidation, and mitochondrial functions.

Results

At thermoneutrality, HFD-fed animals showed increased iBAT lipid fraction (75.3 ± 2% vs. 63.3 ± 1.7%, p < 0.05), elevated plasma glucose and insulin and downregulated UCP1, ATGL, CPT1, and PGC-1α (p < 0.01), indicating impaired oxidative metabolism. Cold exposure significantly reduced iBAT lipid in both CD and HFD groups (p < 0.01) and upregulated functional genes (p < 0.001), restoring mitochondrial functions, lipid oxidation, and thermogenic activity.

Conclusion

HFD feeding caused insulin resistance and impaired iBAT mitochondrial functions and thermogenic activity, due to lipid accumulation. Chronic cold exposure improved insulin sensitivity and restored iBAT oxidative metabolism and mitochondrial functions.