PPAR-α activation counters brown adipose tissue whitening: a comparative study between high-fat– and high-fructose–fed mice

Miranda, Carolline Santos; Silva-Veiga, Flávia Maria; Martins, Fabiane Ferreira; Rachid, Tamiris Lima; Mandarim-de-Lacerda, Carlos Alberto; Souza-Mello, Vanessa

doi:10.1016/j.nut.2020.110791

Cited by 40 publications

(33 citation statements)

References 45 publications

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“…PPAR α is a ligand activated transcription factor and highly expressed in the liver, brown adipose tissue, heart, and kidney ( Braissant et al, 1996 ). Hepatic PPAR α is a major regulator for fatty acid oxidation, lipogenesis, and system inflammation ( Pawlak et al, 2015 ), and increase in PPAR α in brown adipose tissue plays a role in lipogenesis and thermogenesis ( Iizuka et al, 2013 ; Miranda et al, 2020 ). In our current study, RK treatment increased Pparα gene expression in the liver, and this may suggest a role of RK in hepatic lipid metabolism regulation ( Wang et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

Hao

Bello

2021

Front. Physiol.

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Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.

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Section: Discussionmentioning

confidence: 99%

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

Hao

Bello

2021

Front. Physiol.

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“…The BAT lipid droplets were found to be enlarged and associated with reduced UCP1 mRNA expression and protein abundance consistent with whitening of the BAT. This phenotype has been observed in mouse models of diet-induced obesity where it can be reversed with fenofibrate, a PPARα-agonist 50,51 . Interestingly, we previously showed that fenofibrate can prevent CACS in KL mice so the role of BAT in this syndrome needs further study 11,50,51 .…”

Section: Discussionmentioning

confidence: 89%

Blocking ActRIIB signaling and restoring appetite reverses cachexia and improves survival in mice with lung cancer

Queiroz¹,

Ramsamooj²,

Dantas³

et al. 2021

Preprint

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The cancer anorexia-cachexia syndrome (CACS) is a common, debilitating condition with limited therapeutic options. The defining feature of CACS is weight loss, which suggests a state of negative energy balance. It is unclear whether this net reduction in energy is due solely to anorexia or if a combination of anorexia and increased energy expenditure (EE) occurs. To address this question, we induced lung cancer in mice and measured changes in food intake, EE, and body composition. Mice with CACS developed reductions in food intake, spontaneous activity, and EE. There was severe atrophy and markers of metabolic dysfunction in the adipose and skeletal muscle tissues as compared to mice without CACS and pair-fed wild-type mice. We used anamorelin fumarate (Ana), a ghrelin receptor agonist, alone or in combination ActRIIB-Fc, a ligand trap for TGF-β/activin family members, to reverse anorexia and skeletal muscle atrophy, respectively. Ana effectively increased food intake and the combination of drugs increased lean mass, restored spontaneous activity, and improved overall survival. These beneficial effects were limited to female mice. Our findings suggest that multimodal, gender-specific, therapies are needed to reverse CACS.

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“…This finding agrees with the above-mentioned switching of fuel preference in BAT under cold conditions. Moreover, PPARα activation resulted in a reversal of whitening, with the favored thermogenesis being sustained by enhanced β3-adrenergic stimulation, lipolysis, and β-oxidation in BAT of the mice with HFD-induced obesity [93]. However, recent studies have suggested that PPARα is dispensable in thermogenesis.…”

Section: Pparαmentioning

confidence: 99%

PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

Sun

Mao

Chen

et al. 2021

IJMS

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It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to “safely” store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.

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PPAR-α activation counters brown adipose tissue whitening: a comparative study between high-fat– and high-fructose–fed mice

Cited by 40 publications

References 45 publications

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

Blocking ActRIIB signaling and restoring appetite reverses cachexia and improves survival in mice with lung cancer

PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

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