Intermittent and periodic fasting in the treatment of obesity and type 2 diabetes mellitus
Related Articles
Role of pancreatic lipase inhibition in obesity treatment: mechanisms and challenges towards current insights and future directions
The worldwide health emergency of obesity is closely connected to how dietary fats are metabolized, whereas the process is significantly influenced by pancreatic lipase (PL), an enzyme critical for lipid hydrolysis into fatty acids. This narrative review employs a methodological approach utilizing literature searches of PubMed data up to March 2024. The search term criteria encompasses keywords related to the role, mechanism, challenges, and current and future treatments of pancreatic lipase in obesity with an overall references is 106. This paper offers a comprehensive explanation of the role of PL, underlining its significance in the digestive process and lipid imbalances that contribute to obesity and by extension, its impact on obesity development and progression. Additionally, it delves into the dual functionality of the pancreas, emphasizing its impact on metabolism and energy utilization which, when dysregulated, promotes obesity. A focal point of this review is the investigation into the efficacy, challenges, and adverse effects of current pancreatic lipase inhibitors, with orlistat being highlighted as a primary current drug delivery. By discussing advanced obesity treatments, including the exploration of novel anti-obesity medications that target specific biological pathways, this review underscores the complexity of obesity treatment and the necessity for a multifaceted approach. In conclusion, this paper emphasizing the importance of understanding the role of enzymes like pancreatic lipase mechanistic and adopting a multidisciplinary approach to treatment and side effects of current obesity drugs and explore new emerging therapeutic strategies for more effective obesity management.
Effect of broccoli sprout extract and baseline gut microbiota on fasting blood glucose in prediabetes: a randomized, placebo-controlled trial
More effective treatments are needed for impaired fasting glucose or glucose intolerance, known as prediabetes. Sulforaphane is an isothiocyanate that reduces hepatic gluconeogenesis in individuals with type 2 diabetes and is well tolerated when provided as a broccoli sprout extract (BSE). Here we report a randomized, double-blind, placebo-controlled trial in which drug-naive individuals with prediabetes were treated with BSE (n = 35) or placebo (n = 39) once daily for 12 weeks. The primary outcome was a 0.3 mmol l−1 reduction in fasting blood glucose compared with placebo from baseline to week 12. Gastro-intestinal side effects but no severe adverse events were observed in response to treatment. BSE did not meet the prespecified primary outcome, and the overall effect in individuals with prediabetes was a 0.2 mmol l−1 reduction in fasting blood glucose (95% confidence interval −0.44 to −0.01; P = 0.04). Exploratory analyses to identify subgroups revealed that individuals with mild obesity, low insulin resistance and reduced insulin secretion had a pronounced response (0.4 mmol l−1 reduction) and were consequently referred to as responders. Gut microbiota analysis further revealed an association between baseline gut microbiota and pathophysiology and that responders had a different gut microbiota composition. Genomic analyses confirmed that responders had a higher abundance of a Bacteroides-encoded transcriptional regulator required for the conversion of the inactive precursor to bioactive sulforaphane. The abundance of this gene operon correlated with sulforaphane serum concentration. These findings suggest a combined influence of host pathophysiology and gut microbiota on metabolic treatment response, and exploratory analyses need to be confirmed in future trials. ClinicalTrials.gov registration: NCT03763240.
Consensus on the key characteristics of metabolism disruptors
Metabolism-disrupting agents (MDAs) are chemical, infectious or physical agents that increase the risk of metabolic disorders. Examples include pharmaceuticals, such as antidepressants, and environmental agents, such as bisphenol A. Various types of studies can provide evidence to identify MDAs, yet a systematic method is needed to integrate these data to help to identify such hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we developed 12 KCs of MDAs based on our knowledge of processes underlying metabolic diseases and the effects of their causal agents: (1) alters function of the endocrine pancreas; (2) impairs function of adipose tissue; (3) alters nervous system control of metabolic function; (4) promotes insulin resistance; (5) disrupts metabolic signalling pathways; (6) alters development and fate of metabolic cell types; (7) alters energy homeostasis; (8) causes inappropriate nutrient handling and partitioning; (9) promotes chronic inflammation and immune dysregulation in metabolic tissues; (10) disrupts gastrointestinal tract function; (11) induces cellular stress pathways; and (12) disrupts circadian rhythms. In this Consensus Statement, we present the logic that revealed the KCs of MDAs and highlight evidence that supports the identification of KCs. We use chemical, infectious and physical agents as examples to illustrate how the KCs can be used to organize and use mechanistic data to help to identify MDAs.
Cellular and molecular mechanisms underlying obesity in degenerative spine and joint diseases
Degenerative spine and joint diseases, including intervertebral disc degeneration (IDD), ossification of the spinal ligaments (OSL), and osteoarthritis (OA), are common musculoskeletal diseases that cause pain or disability to the patients. However, the pathogenesis of these musculoskeletal disorders is complex and has not been elucidated clearly to date. As a matter of fact, the spine and joints are not independent of other organs and tissues. Recently, accumulating evidence demonstrates the association between obesity and degenerative musculoskeletal diseases. Obesity is a common metabolic disease characterized by excessive adipose tissue or abnormal adipose distribution in the body. Excessive mechanical stress is regarded as a critical risk factor for obesity-related pathology. Additionally, obesity-related factors, mainly including lipid metabolism disorder, dysregulated pro-inflammatory adipokines and cytokines, are reported as plausible links between obesity and various human diseases. Importantly, these obesity-related factors are deeply involved in the regulation of cell phenotypes and cell fates, extracellular matrix (ECM) metabolism, and inflammation in the pathophysiological processes of degenerative spine and joint diseases. In this study, we systematically discuss the potential cellular and molecular mechanisms underlying obesity in these degenerative musculoskeletal diseases, and hope to provide novel insights for developing targeted therapeutic strategies.
Raptin, a sleep-induced hypothalamic hormone, suppresses appetite and obesity
Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.
Responses