Despite the use of caloric deficit through changes in diet or physical activity, the obese population has enormous difficulties in losing or maintaining weight and/or improving certain endocrine parameters. Therefore, considering the attributed effects of polyphenols in an obese population, different products could helping improve the previous results related to obesity treatment.
The scientific literature about polyphenols has been focused on their antioxidant capacity, but also in their possible use for the treatment of obesity (28). In this regard, the present clinical research reports the efficacy of the polyphenols contained in an Lc-Hs extract.
Hunger and satiety are regulated in the hypothalamus by complex network of neural pathways and the neuroendocrine system through central and peripheral molecular signals, gastrointestinal hormones, cytosines, metabolic intermediates, and nutrients. The regulating system can may have an orexigenic effect by activating anabolic pathways responsible for maintaining or gaining weight through mechanisms which induce hunger and stimulate appetite. On the other hand, the regulating system can exert an anorexigenic effect, stimulating catabolic pathways that promotes weight loss, through mechanisms that increase energy expenditure and decrease food intake by gastric filling and increased satiety (29).
The most noticeable effect observed during the monitoring of food intake was decreased satiety. Satiety is a necessary parameter regulating body weight control, since it is the most effective factor to achieve progressive and successful long-term weight loss. One of the most common factors during weight loss in obese or overweight patients is anxiety caused by a reduction in the volume of dietary food, which can lead to excessive intake. This situation is one of the main factors that compromise the effectiveness of the protocols of weight loss and lifestyle change established for the treatment of obesity and overweight.
Judging by the results of the present study, chronic intake of a nutraceutical Lc-Hs extract during 8 weeks increase satiety in overweight and obese population. The most noticeable effect was an increase in SQ, reducing caloric intake throughout the day. Is important to note that higher values represent greater satiety and lower values less satiety (30). SQ is considered a valid indicator of satiety due to considers the AS before meals and the caloric content of food. In addition, has been shown to be positively associated with energy intake (31, 32) being the higher SQ value, the lower caloric consumption, as occurs in the present study. Another interesting insight is the observed decrease are AS during at least two hours after meal intake, and reduced AUC from baseline to 240 -being more pronounced from baseline to minute 60-. Furthermore, due to similar protein content after ad-libitum intake in both groups (Table 2), it can be can affirmed that lower caloric intake and improvement in SQ and satiety do not relies on higher protein intake, which is known for its greater satiating capacity (11). Recognizing that satiety is defined as the interval between meals as a function of elapsed time, and that it can be used to predict the next feeding episode (33), SQ in seems to predict ad-libitum intake in the next 3 hours, a normal time period between meals.
Results observed for satiety and hunger sensation are in agreement previous studies in overweight population that reported an improvement in satiety sensation the treatment with the same Hs-LC extract during 8 weeks (18). Other authors have reported that different polyphenols can exert a synergistic effect to enhance their potential benefit (34, 35). However, the bioavailability in the intestinal tract should be considered (36).
Research on polyphenols against obesity seems to be due to various mechanisms of action as; lower food intake, decrease lipogenesis, increase lipolysis, stimulate fatty acid β-oxidation, inhibit adipocyte differentiation and growth, attenuate inflammatory responses and suppress oxidative stress (28, 37). Mechanisms include; Increased peroxisome proliferator-activated receptor (PPAR-γ) which promotes acid β-oxidation (38), inhibition of synthesis of malonyl-Coa (39) fatty acids precursor, increased CPT-1 protein which facilitate transport of fatty acids into mitochondria (38), activation of AMP-activated protein kinase (AMPK) pathway improving the glucose uptake in the cell (40) and thus insulin resistance. For example, scientific evidence has sown that certain plan-derivate such a Hibiscus sabadarrifa or Lippia citriodora can modulate different metabolic pathways and have certain effects activating the AMPK pathway, favoring lipolysis and fat loss (9, 17).
The regulation of AS, hunger and satiety occur in the hypothalamus, main regulatory area in central nervous systems. The arcuate nucleus is the hypothalamus region that participates in the control of food intake and have specific receptors for a wide variety of hormones and peptides that circulate in blood (41). After analyzing the different blood samples, no long-term inter-subject significant differences were observed in different hormones such as insulin, adiponectin, PYY or Ghrelin. However, there are some tendencies that should be mentioned.
Ghrelin is synthesized in the gastric fundus and bloating of the stomach in the presence of a large volume of food (42) reduces its plasmatic concentration. In the present research, Ghrelin showed a downward trend that varies between Pla and Lc-Hs groups. In fact, Pla treatment led to acutest diminution of ghrelin concentration during the 90 first minutes after meal intake-. In turn, Lc-Hs treatment was not as effective for reducing ghrelin synthesis in the first 90 minutes after meal intake as Pla. However, it was able to achieve a homogeneous and stable decrease (plateau shape) along the 240 minutes of plasmatic monitorization. As observed previously, volunteers treated with Lc-Hs reduced their caloric consumption, which can be a consequence of the reduction in the volume of food consumed that would lead to minor reduction on plasmatic ghrelin (greater plasmatic concentration). Therefore, Lc-Hs treatment was able to reduce caloric intake and food volume, while reducing Ghrelin concentration homogeneously for 240 minutes which can explain the reduction on hunger observed above. Despite not obtaining statistically significant results, it seems evident that treatment with Lc-Hs is able to reduce food intake, as shown in adlibitum intake, appetite sensation and Ghrelin concentration in overweight and obese patients. The present data reinforces the idea that an adjuvant treatment with polyphenols can favorably affect glucose intake and regulation, adipogénesis, lipolysis, lipid metabolism, appetite control and improve pathologies related to obesity due to AMPK pathway modulation (9, 18). As well as the practice of physical exercise that help to reach caloric deficit, may be the best strategy for the treatment of obesity given the nature of the disease (43).
The determination of Leptin resulted in decreased concentration in Lc-Hs group (p > 0,05), showing certain intra-subject significant decrease (p < 0,05) between baseline and final measurements. The same tendency was not observed in the acute part of the study due to the long-term effect of that hormone. Leptin is mainly synthesized in adipose tissue and is able to inhibit food intake, being the most important hormone for long-term maintenance of body weight. However, obese population may present Leptin resistance, mainly due to lipid-related inflammation (44). Considering this premise, the decrease in leptin levels can be explained by the loss of fat mass observed in patients treated with Lc-Hs, so that the secretory capacity of leptin would also be reduced due to a lower amount of adipose tissue. That reduction in adipose tissue could also be responsible of the decrease in low-grade inflammation that predominates in overweight or obese patient, which is part-responsible of leptin resistance (45). Despite the reduction in leptin levels, the satiety sensation of the volunteers treated with the Lc-Hs extract increased in comparison with the Pla group. This could be a consequence of reduced Leptin resistance, which leads at least the same effects on hunger control with minor Leptin secretion (9, 44).
Likewise, the variation during feeding test of adiponectin is not marked but noticeable. The mechanisms underlying obesity-related reduction in plasmatic adiponectin have not yet been described in detail. Moreover, obese inflamed adipose tissues have been shown to reduce adiponectin secretion from adipocytes, while fat mass and the number of adipocytes in the whole body markedly increase with obesity (46). The long-term study of adiponectin in the present study reported similar values than the previous literature regardless body fact variation along the long-term study, showing that caloric diet variation does not alter adiponectin levels over time (38, 47). It has also been reported that low caloric diets do not varies plasmatic adiponectin levels regarding short (39, 48) and intermediate (40, 49) time periods. However, other authors reported that long-term interventions increase plasmatic adiponectin, improving abdominal fat distribution and lipid metabolism independently of weight change (50). In fact, the mechanism underlying adiponectin and its role in obesity needs more study. Short-term part of the present study reported continued reduction until the ad-libitum lunch for both Pla and Lc-Hs. Meanwhile, previous studies have seen an increase in adiponectin (51). Therefore, the variation of adiponectin in the present study seems to be influenced in both short and long periods, showing different trends.
Furthermore, in obese subjects, GLP-1 (anorexigenic satiating incretin) concentration is low, so a decrease could be expected in obese and overweight population (25, 41). The acute part of the present study revealed similar values for both Pla and Lc-Hs groups, with no differences between them. Almost all the hormones presented similar baseline values, as shown in Fig. 9, in order to reach more significant results GLP-1 values was standardized from baseline. The standardization was necessary due to the differences observed at baseline that could be misleading. As can be observed, GPL-1 increased in the Lc-Hs group after the treatment, improving fullness and satiety that could explain the excellent SQ observed in that group. Therefore, in the present study GLP-1 seems to be mayor factor controlling satiety and desire to eat.
In turn, the long-term part of the study showed some minor differences, but there were not noticeable. GLP-1 is synthesized in intestinal L cells whose secretion depends on the presence of nutrients in the lumen of the small intestine. Once GLP-1 reaches circulation, it has a half-life of a few minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4 (52). Therefore, the long-term evolution of GLP-1 does not provide as much information about the control of hunger and satiety as does the short-term evolution. In fact, the scientific literature on the long-term effects of GLP-1 is an area yet to be explored.
Due to the improvements in lipid profile observed in in vitro an animal models (53), it seems desirable to measure these parameter in a human-based study. Meanwhile, glucose level was not improved during the present study; however, a significant reduction of glycated hemoglobin was observed in volunteers treated with Lc-Hs but not in Pla group. In contrast, LDL Cholesterol and HDL Cholesterol varied significantly after the treatment with Lc-Hs, leading to minor and higher plasmatic levels respectively. Meanwhile, total cholesterol showed a downward trend, but there was not found any significant variation for triglycerides. That variation in lipid profile may be due to the substances and antioxidant effects of the polyphenols present in Lc-Hs extract specially due to anthocyanins content (54, 55). In this study significant reductions in lipid levels were seen in hyperlipidemcic subjects after consumption of Hibiscus sabdariffa (56).
Body composition was improved in the Lc-Hs group with a reduction in fat mass, not observing changes in FFM or BMI. It is essential to differentiate FFM from lean mass, due to many people misinterpret FFM value as if it were a muscle mass overestimating that value (26). FFM includes muscle mass, bone mass, skin mass, and residual mass. There were also no changes in quality of life test, as well as adverse al
tri in liver or kidney function after product intake (57). In this study, researchers found a reduction in fat mass (especially in the torso) after the consumption of 84 days of a Lc-Hs extract in similar population (58). In the present study, the BMI of the volunteers did not change along the whole study (p > 0,05); however, the reduction on fat mass and the increase in FFM reveals that the treatment with Lc-Hs is a possible treatment that prevents sarcopenia (59, 60).
Therefore, a polyphenolic extract based on Lippia citriodora and Hibiscus sabdarrifa improves the regulation of appetite in overweight population, mainly satiety. On the other hand, the lower leptin values were expected due to reduction in fat mass of subjects. In addition, the maintenance of FFM can produce a decrease in basal metabolism of the volunteers, favoring a possible lon-term weight reduction. This, together with hormonal and lipidemic changes observed in the study, may contribute to improvements in health.