Roles of exogenous bioactive peptides in obesity and obesity-related diseases: A review

Obesity is now commonly seen worldwide and across all age groups. Obesity is the result of excessive nutrient intake often from sources which are highly processed which have a high energy-to-nutrient ratio. These dietary excuses are then compounded by decreased physical activity levels. Whilst these aetiological influences are thought to be easily modifiable, the reality is that individuals are becoming increasingly over-weight and obesity related diseases are posing more problems than ever before. Obesity has many metabolic consequences including, insulin resistance and predisposition for the development of chronic diseases such as cancers, autoimmune diseases, and type 2 diabetes (T2D). Diabetes then incurs further vascular complications in organs that have intricate microvascular networks such as those within, neurons, eyes and kidneys, leading to gangrenous limbs and amputations, cataracts and blindness, renal failure. Of course the ultimate complication of diabetes is early death, normally as a result of cardiac disease and heart failure. Receptor for advanced glycation end products (RAGE) and its modulation of downstream pathways are recognised pathological contributors to the vascular complications of diabetes including renal disease. There is increasing evidence that obesity is an independent risk factor for kidney disease, in particular in the context of type 2 diabetes. However, the mechanisms by which obesity contributes to kidney disease remain to be determined. Estradiol (17-β-estradiol) has been shown to confer protection against renal and cardiovascular disease when it is the major biologically active estrogen. In obesity, white adipose tissue deposits secrete another estrogen isoform called estrone, which alters the balance of estrogens. Imbalances in estradiol to estrone are the development of obesity related diseases. At the time of beginning this thesis, there were no drugs available for the specific treatment of obesity related renal diseases. Some treatments are borrowed from type 2 diabetes and chronic kidney disease and have modest effects on excretion of albumin or target blood pressure lowering pathways. Others directly target obesity, leading to weight loss although these are often temporary. Therefore this thesis examines the development of obesity related renal disease. I have examined the role of excessive adipose tissue deposition and the ability of estrogens to modulate the receptor for advanced glycation end products (RAGE), to discover potential therapeutic targets to control the growing problem of obesity related kidney disease.

Adipose tissue develops lipids, aberrant adipokines, chemokines, and pro-inflammatory cytokines as a consequence of the low-grade systemic inflammation that characterizes obesity. This low-grade systemic inflammation can lead to insulin resistance (IR) and metabolic complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Although the CXC chemokines consists of numerous regulators of inflammation, cellular function, and cellular migration, it is still unknown that how CXC chemokines and chemokine receptors contribute to the development of metabolic diseases (such as T2D and NAFLD) during obesity. In light of recent research, the objective of this review is to provide an update on the linkage between the CXC chemokine, obesity, and obesity-related metabolic diseases (T2D and NAFLD). We explore the differential migratory and immunomodulatory potential of CXC chemokines and their mechanisms of action to better understand their role in clinical and laboratory contexts. Besides that, because CXC chemokine profiling is strongly linked to leukocyte recruitment, macrophage recruitment, and immunomodulatory potential, we hypothesize that it could be used to predict the therapeutic potential for obesity and obesity-related diseases (T2D and NAFLD).

Cross-sectional analysis of visceral adipose tissue associations with obesity-related disease

Comparative biological evaluation and identification of multifunctional endogenous and exogenous bioactive peptides in different matured Izmir Tulum cheeses

In recent years, some exogenous bioactive peptides have been shown to have promising anti-aging effects. These exogenous peptides may have a mechanism similar to endogenous peptides, and some can even regulate the release of endogenous active peptides and play a synergistic role with endogenous active peptides. Most aging studies use rodents that are easy to maintain in the laboratory and have relatively homogenous genotypes. Moreover, many of the anti-aging studies using bioactive peptides in rodent models only focus on the activity of single endogenous or exogenous active peptides, while the regulatory effects of exogenous active peptides on endogenous active peptides remain largely under-investigated. Furthermore, the anti-aging activity studies only focus on the effects of these bioactive peptides in individual organs or systems. However, the pathological changes of one organ can usually lead to multi-organ complications. Some anti-aging bioactive peptides could be used for rescuing the multi-organ damage associated with aging. In this paper, we review recent reports on the anti-aging effects of bioactive peptides in rodents and summarize the mechanism of action for these peptides, as well as discuss the regulation of exogenous active peptides on endogenous active peptides.

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor alpha and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.

Nonalcoholic fatty liver disease (NAFLD), the major reason for abnormal liver function in the Western world, is associated with obesity and diabetes and is characterized by insulin resistance (IR). IR is regulated by mediators released from cells of the immune system or adipocytes and proinflammatory cytokines such as tumor necrosis factor-α (TNFα). The importance of TNFα in human and animal fatty liver diseases, both caused by genetic manipulation and overnutrition, has been shown convincingly. Furthermore, neutralization of TNFα activity improves IR and fatty liver disease in animals. Adiponectin is a potent TNFα-neutralizing and anti-inflammatory adipokine and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR. Anti-inflammatory effects of adiponectin are exerted both by suppressing TNFα synthesis and by induction of anti-inflammatory cytokines such as interleukin-10 or interleukin-1–receptor antagonist. Therefore, the balance between various mediators, either derived from the immune system or adipose tissue, appears to play an important role in hepatic and systemic insulin action and in the development of fatty liver disease.

Selective Insulin and Leptin Resistance in Metabolic Disorders

The links between gut microbiota and obesity and obesity related diseases

The main manifestation of obesity is persistent low-level inflammation and insulin resistance, which is an important factor inducing or promoting other obesity-related diseases. As a proinflammatory programmed cell death, pyroptosis plays an important role, especially in the activation and regulation of the NLRP3 inflammasome pathway. Pyroptosis is associated with the pathogenesis of many chronic inflammatory diseases and is characterized by the formation of micropores in the plasma membrane and the release of a large number of proinflammatory cytokines. This article mainly introduces the main pathways and key molecules of pyroptosis and focuses on the phenomenon of pyroptosis in obesity. It is suggested that the regulation of pyroptosis-related targets may become a new potential therapy for the prevention and treatment of systemic inflammatory response caused by obesity, and we summarizethe potential molecular substances that may be beneficial to obesity-related inflammatory diseases through target pyroptosis.

Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.

Do women with PCOS have a unique predisposition to obesity?

Hypovitaminosis D and obesity represent two pandemic conditions sometimes associated with each other. Although it is known that there is a close relationship between these two health problems, the underlying pathophysiological mechanism has not yet been fully clarified. In fact, on the one hand, obesity per se seems to involve low circulating levels of vitamin D due to low sun exposure, physical activity, and intake of foods rich in vitamin D, volumetric dilution and sequestration in the adipose tissue. Conversely, since preadipocytes and adipocytes express the receptors and are involved in the metabolism of vitamin D it would seem that low levels of this vitamin may be involved in adipogenesis and therefore in the development of obesity. This connection is extremely important when considering obesity-related diseases. In fact, low vitamin D levels and severe obesity are significantly associated with some cardio-metabolic risk factors, including high Body Mass Index, waist circumference, blood pressure, impaired lipid and glycemic profile and insulin resistance, as they would seem associated with worse cardiovascular outcomes and higher cancer incidence and mortality. Therefore, the purpose of this review was to examine the recent evidence linking low vitamin D status, obesity and obesity-related diseases, highlighting the scientific achievements and the gaps to be filled with further investigations.

Fat accumulates within the body of a person who is overweight or obese until many small physiological changes accumulate to a tipping point where adipose tissue becomes “sick.” Adisopathy or “sick fat” leads to a host of other obesity-related diseases. In this chapter the development of adisopathy is discussed in detail with an emphasis on insulin resistance and the role of mitochondria, hormones, inflammatory markers and leptin. This chapter describes the mechanisms of disease for prediabetes and type 2 diabetes and explores the concept of metabolic syndrome. It also explains the pathophysiology of obesity as it relates to non-alcoholic fatty liver disease (NAFLD). The chapter ends with specific discussions about the relationships between obesity and other obesity-related diseases, including hypertension, dyslipidemia, atherosclerosis, coronary heart disease and stroke.

Obesity represents one of the major public health issues threatening the global health and promoting chronic metabolic disorders, including type 2 diabetes, insulin resistance (IR), hyperlipidemia, hypertension, polycystic ovary syndrome, metabolic-associated fatty liver disease (MAFLD), and others. Ferroptosis, a novel form of cell death, is a programmed cell death induced by iron-dependent lipid peroxidation. It is characterized by excessive iron accumulation and unregulated lipid peroxidation. The activity of ferroptosis is modulated by multiple factors such as iron, reactive oxygen species, and over 98 unsaturated fatty acids. Mounting evidence indicates that ferroptosis plays a crucial role in obesity-related chronic metabolic diseases like type 2 diabetes, IR, hyperlipidemia, hypertension, polycystic ovary syndrome, and MAFLD. Clarifying the molecular mechanism of ferroptosis may discover potential therapeutic targets for the treatment of these diseases. This article comprehensively reviews the role, pathogenesis, prevention, treatment strategies, current research gaps and future development directions of ferroptosis in obesity-related chronic metabolic diseases have been thoroughly discussed, and novel perspectives for the future treatment and research of ferroptosis in these diseases carefully provided. It points out directions for basic research on ferroptosis, raises urgent needs for developing precise intervention strategies, and provides new insights into the treatment and study of obesity-related chronic metabolic diseases in the future.