Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity

Abstract

Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to "unhealthy obesity". In a previous work, we described a pomegranate extract (PomE) rich in punicalagines to augment markers of browning and thermogenesis in human differentiated adipocytes and to augment the oxidative respiratory capacity in human differentiated myocytes. Herein, we have conducted a preclinical study of high-fat-diet (HFD)-induced obesity where PomE augments the systemic energy expenditure (EE) contributing to a reduction in the low grade of chronic inflammation and insulin resistance associated to obesity. At the molecular level, PomE promotes browning and thermogenesis in adipose tissue, reducing inflammatory markers and augmenting the reductive potential to control the oxidative stress associated to the HFD. PomE merits further investigation as a complementary approach to alleviate obesity, reducing the low grade of chronic inflammation and metabolic stress.

Keywords: energy expenditure; meta-inflammation; obesity; pomegranate extract; thermogenesis.

Figure 1

Shows the study workflow indicating the biochemical and molecular determinations (insulin and glucose tolerance tests; densitometry, indirect calorimetry, and the cold chamber exposition for heat stress).

Figure 2

Comparison of food intake (A) and weight (B) of the animals of ND-control group with that of HFD-control and HFD-PomE groups. Statistically significant values are indicated with asterisks based on their p-value, ** p < 0.01, *** p < 0.001.

Figure 3

Metabolic phenotyping of glucose and insulin homeostasis in the different groups. Insulin (A) and glucose (B) tolerance tests were performed at the indicated hours. The area under the curve (AUC) is also represented. (C) HOMA/IR values for the different groups. (D) Fasting insulin levels for the different groups. Asterisks refer to the comparison with the corresponding control ND group, and between the HFD-PomE and HFD-control groups. Statistically significant values are indicated with asterisks based on their p-value, *, p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 4

(A) Energy expenditure, (B) volume of oxygen (VO₂), and (C) volume of CO₂ (VCO₂) parameters in HFD-PomE and HFD-control groups (N = 8). Statistically significant values are indicated with asterisks based on their p-value, * p < 0.05, ** p < 0.01.

Figure 5

Mice rectal temperature after cold exposition in HFD-PomE (N = 4–6) and HFD groups (N = 4–6). Statistically significant values are indicated with asterisks based on their p-value, * p < 0.05.

Figure 6

Gene expression levels of targets related to thermogenesis in the different types of adipose tissues (brown (BAT), inguinal white (iWAT), and epididymal white (eWAT) adipose tissues), in ND, HFD-control and HFD-PomE groups, exposed or not to cold stress (N = 4–8). Statistically significant values are indicated with asterisks based on their p-value, * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 7

Gene expression levels of the thermogenic IL17AR in the (A) inguinal white (iWAT) and (B) epididymal white (eWAT) adipose tissues, and (C) the myokine IL6 in white (WM) and red (RM) muscle tissues, of HFD-control and HFD-PomE groups, exposed or not to cold stress (N = 4–8). Statistically significant values are indicated with asterisks based on their p-value, ** p < 0.01.

Figure 8

Gene expression levels of genes related to glycolysis and redox homeostasis in brown adipose tissue (BAT) and in the white muscle tissues of HFD-control and HFD-PomE groups, exposed or not to cold stress (N = 4–8). Statistically significant values are indicated with asterisks based on their p-value, ** p < 0.01.

Figure 9

Proposed model of PomE to alleviate the metabolic stress associated to HFD-induced obesity.