Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

Abstract

To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.

Ghrelin modulates hypothalamic fatty acid-sensing and control of food intake in rainbow trout

“…This orexigenic effect is mediated by changes in fatty acid metabolism and other parameters related to fatty acid-sensing systems that basically reverse those elicited by raised levels of LCFA (Ló pez et al 2008, Sangiao-Alvarellos et al 2010, Martins et al 2013, Gao et al 2013, Stark et al 2015. Besides the role of GHRL in food intake regulation, this hormone has been also involved in the control of glucose and lipid homeostasis and metabolism (Sangiao-Alvarellos et al 2010, Ratner et al 2015 and modulation of hormone release (Carreira et al 2013), among others (Sato et al 2014, Müller et al 2015. GHRL has been also identified in a number of fish species, including rainbow trout (Oncorhynchus mykiss), Japanese eel (Anguilla japonica), sea bass (Dicentrarchus labrax), Atlantic salmon (Salmo salar), zebrafish (Danio rerio), goldfish (Carassius auratus), tilapia (Oreochromis mossambicus) and channel catfish (Ictalurus punctatus) (Kaiya et al 2008, Kang et al 2011.…”

Supplementation of the Flavonoid Myricitrin Attenuates the Adverse Metabolic Effects of Long-Term Consumption of a High-Fat Diet in Mice

“…38,39 However, fasting increases fatty acid oxidation in the WAT, 40,41 and upregulated fatty acid oxidation capacity in the WAT plays important roles in protecting against obesity and its metabolic complications. [42][43][44] Impaired fatty acid oxidation resulting from lower CPT1b mRNA expression levels in the WAT is suggested to contribute to excessive fat accumulation in obese rats. 41 Pharmacological inhibition of fatty acid oxidation can exacerbate cytokine release and impair insulin activities, 43 while upregulation of fatty acid oxidation in 3T3-L1 adipocytes through constitutive overexpression of CPT1a results in reduced triglyceride content, insulin resistance, and inflammation.…”

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

“…CPT consists of 2 mitochondrial enzymes, including CPT1 and CPT2, in which CPT1 facilitates acyl‐CoA conversion into acylcarnitine, which enters the inner mitochondrial membrane, while CPT2 promotes the release of acyl‐CoA . The expression of CPT1β, a subtype of CPT1, has been found to be decreased in an obese rat model, and this decrease impairs the oxidative capacity of the rats and contributes to their fat accumulation . Moreover, obese individuals have been shown to have reduced CPT‐1 activity, which decreases the level of FAO .…”

“…51 The expression of CPT1β, a subtype of CPT1, has been found to be decreased in an obese rat model, and this decrease impairs the oxidative capacity of the rats and contributes to their fat accumulation. 52 Moreover, obese individuals have been shown to have reduced CPT-1 activity, which decreases the level of FAO. 53,54 Treatment with etomoxir, an inhibitor of CPT, potently blocks the M2 polarization of macrophages.…”