Dietary Potassium Synergistically Enhances Anti-Obesity Efficacy of Garcinia Cambogia Complex in High-Fat Diet-Induced Obese Mice

Abstract

Obesity is a global health problem associated with several metabolic disorders. Conventional dietary supplements such as Garcinia cambogia, catechin, and conjugated linoleic acid (GC complex) are widely used for weight loss but raise concerns about long-term efficacy and safety. Recent advances in nutritional research suggest that combining dietary mineral elements might enhance obesity therapeutic outcomes. The objective of this study is to investigate the potential synergistic effects of potassium in combination with GC complex in a mouse model of high-fat diet (HFD)-induced obesity. When administered daily orally for 12 weeks, the HFD+GC+Potassium group exhibited synergistically reduced adipocyte size in both white and brown adipose tissue compared to the HFD group, indicating a reduction in fat storage. In addition, HFD+GC+Potassium group exhibited a marked improvement in metabolic profiles, characterized by reduced fasting glucose and total cholesterol levels without toxicity, compared with HFD group. Histological analyses confirmed the effectiveness of the treatment, showing marked reductions in hepatic steatosis and lipid accumulation, as evidenced by H&E and Oil Red-O staining in the HFD+GC+Potassium group. Significantly, the study showed that potassium supplementation in combination with GC complex improved lipid metabolism and energy expenditure by increasing the expression of phosphorylated acetyl-CoA carboxylase 1 (p-ACC1) and carnitine palmitoyltransferase I (CPT1), while decreasing the levels of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1) through IGF1R/PI3K/AKT/GSK3β axis. These findings suggest that the combination of GC complex and dietary potassium may offer a synergistic effect and a safe strategy for managing obesity by reducing fat accumulation and enhancing metabolic health.

Keywords: High fat; Lipid metabolism; Obesity; Potassium.

Fig. 1

The synergistic effect of potassium supplement on body weight induced by high-fat diet. (A) A schematic representation of the experimental design showing four groups of C57BL/6 mice (ND, HFD, HFD+GC, and HFD+GC+Potassium) fed with different diets for 12 weeks. (B) The C57BL/6 mice were fed with 60% high fat diet for 12 weeks. Body weights were measured weekly. Data are presented as mean ± SD (n=5-7 in each group). The following abbreviations are used throughout the figures: ND, mice fed with normal diet; HFD, mice fed with 60% fat diet; HFD+GC, mice fed with GC complex and 60% fat; HFD+GC+Potassium, mice fed with a combination of GC complex, potassium, and 60% fat diet. *p<0.05 and **p<0.01 versus HFD group.

Fig. 2

The synergistic effect of potassium supplement on fat weights and size. (A) Representative photographs of mice from each group at the end of 12 weeks. (B) Change in the size of epididymal fat from each group at the end of 12 weeks. (C) Weight of epididymal fat, perirenal fat, and brown fat. Data are presented as mean ± SD (n=5-7 in each group). The significance of the difference between the four groups was analyzed by one-way ANOVA analysis of variance. **p<0.01 and ***p<0.001 versus HFD group.

Fig. 3

Serum metabolic effects and safety profile of potassium supplementation in combination with the GC complex. After 12 weeks of treatment, blood was collected from mice. (A, B) The levels of blood glucose, insulin, T-CHO, TG, and LDL were determined in the ND, HFD, HFD+GC and HFD+GC+Potassium groups. (C) The level of ALT, BUN, and CRE were determined to assess potential toxicology. There were no significant changes in ALT, CRE or BUN, indicating that the combined GC and potassium did not show hepatic or renal toxicity. Data are presented as mean ± SD (n=5-7 in each group). Significant difference was determined by one-way analysis of variance. *p<0.05 and **p<0.01 versus HFD group.

Fig. 4

The synergistic effect of potassium supplement on lipid accumulation in liver and adipose tissues. (A) Hematoxylin and eosin (H&E) staining of liver, epididymal white-adipose tissue, and inter-scapular brown adipose tissue. Oil staining of liver sections from the same groups and the quantification of hepatic steatosis. (B) Quantification of lipid droplet area in liver, WAT, and BAT. Values are expressed as mean ± SD (n=5 per group). (C) Western blot analysis of lipid metabolism-related proteins including FAS, CPT1, UCP-1, and PGC1α in liver, WAT, and BAT. β-actin was used as a loading control. The significance of the difference between the four groups was analyzed by one-way ANOVA analysis of variance. *p<0.05 and ***p<0.001 versus HFD group.

Fig. 5

Inhibition of lipogenesis by potassium supplementation through the IGF1R/PI3K/AKT/GSK3β signaling in combination with the GC complex. (A) The immunohistochemical staining of FAS, SREBP1, CPT1 and p-ACC1 in liver sections from each group. (B) Quantification of immunohistochemical (IHC) scoring for positive staining of the four proteins. The expression of lipogenesis-related proteins was significantly decreased by potassium and GC complex compared to the HFD group. Values are expressed as mean ± SD (n=5 per group). (C) Western blot analysis of IGF1R, PI3K, p-AKT, p-GSK3β in liver tissue of each group. β-actin was used as a loading control. The significance of the difference between the four groups was analyzed by one-way ANOVA analysis of variance. *p<0.05 and **p<0.01 versus HFD group.

Fig. 6

A schematic representation of proposed mechanism of synergistic anti-obesity effects of potassium and GC complex. The combination attenuates lipogenesis via the IGF1/PI3K/AKT/GSK3β pathway. IGFR1, Insulin-like growth factor 1 receptor; PI3K, Phosphoinositide 3-kinase; AKT, Protein kinase B; GSK3β, Glycogen synthase kinase-3 beta.