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Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent condition affecting approximately a quarter of the global population. It is associated with increased morbidity, mortality, economic burden, and healthcare costs. The disease is characterized by the accumulation of lipids in the liver, known as steatosis, which can progress to more severe stages such as steatohepatitis, fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). This review focuses on the mechanisms that contribute to the development of diet-induced steatosis in an insulin-resistant liver. Specifically, it discusses the existing literature on carbon flux through glycolysis, ketogenesis, TCA (Tricarboxylic Acid Cycle), and fatty acid synthesis pathways in NAFLD, as well as the altered canonical insulin signaling and genetic predispositions that lead to the accumulation of diet-induced hepatic fat. Finally, the review discusses the current therapeutic efforts that aim to ameliorate various pathologies associated with NAFLD. [ABSTRACT FROM AUTHOR]

The sugar alcohol erythritol is a relatively new food ingredient. It is naturally occurring in plants, however, produced commercially by fermentation. It is also produced endogenously via the pentose phosphate pathway (PPP). Consumers perceive erythritol as less healthy than sweeteners extracted from plants, including sucrose. This review evaluates that perspective by summarizing current literature regarding erythritol's safety, production, metabolism, and health effects. Dietary erythritol is 30% less sweet than sucrose, but contains negligible energy. Because it is almost fully absorbed and excreted in urine, it is better tolerated than other sugar alcohols. Evidence shows erythritol has potential as a beneficial replacement for sugar in healthy and diabetic subjects as it exerts no effects on glucose or insulin and induces gut hormone secretions that modulate satiety to promote weight loss. Long-term rodent studies show erythritol consumption lowers body weight or adiposity. However, observational studies indicate positive association between plasma erythritol and obesity and cardiometabolic disease. It is unlikely that dietary erythritol is mediating these associations, rather they reflect dysregulated PPP due to impaired glycemia or glucose-rich diet. However, long-term clinical trials investigating the effects of chronic erythritol consumption on body weight and risk for metabolic diseases are needed. Current evidence suggests these studies will document beneficial effects of dietary erythritol compared to caloric sugars and allay consumer misperceptions. [ABSTRACT FROM AUTHOR]

As the largest "immune organ" of human beings, the gut microbiota is symbiotic and mutually beneficial with the human host, playing multiple physiological functions. Studies have long shown that dysbiosis of gut microbiota is associated with almost all human diseases, mainly including type II diabetes, cancers, neurodegenerative diseases, autism spectrum disorder, and kidney diseases. As a novel and potential biological medicine for disease prevention, intervention and drug sensitization, the gut microbiota has attracted more and more attention recently. Although the gut microbiota is a comprehensive microbial community, several star bacteria have emerged as possible tools to fight against various diseases. This review aims to elucidate the relevance of gut microbiota dysbiosis with disease occurrence and progression, and mainly summarizes four well-known genera with therapeutic and sensitizing potential, Akkermansia, Bifidobacterium, Lactobacillus and Parabacteroides, thoroughly elucidate their potential value as biological drugs to treat diverse disease. [ABSTRACT FROM AUTHOR]

Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets; low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D replete and one deficient. Visceral fat, hepatic adiposity, and insulin resistance were measured after five and a half weeks. Vitamin D deficiency, independent of dietary fat, increased hepatic fat accumulation in both sexes (p = 0.003), although did not increase hepatic expression of interleukin-6 (p = 0.92) or tumor necrosis factor-α (p = 0.78). Males were observed to have greater insulin resistance (glucose area under the curve: p < 0.001, homeostatic model assessment for insulin resistance: p = 0.046), and have greater visceral adiposity (p < 0.001), while female mice had greater hepatic fat accumulation (p < 0.001). This study is the first to demonstrate vitamin D deficiency alone can cause hepatic accumulation while also being the first to observe higher liver fat percentages in female mice. [ABSTRACT FROM AUTHOR]

The need to refine rodent models of human-related disease is now being recognized, in particular the rearing environment that can profoundly modulate metabolic regulation. Most studies on pregnancy and fetal development purchase and transport young females into the research facility, which after a short period of acclimation are investigated (Gen0). We demonstrate that female offspring (Gen1) show an exaggerated hyperinsulinemic response to pregnancy when fed a standard diet and with high fructose intake, which continues throughout pregnancy. Markers of maternal hepatic metabolism were differentially influenced, as the gene expression of acetyl-CoA-carboxylase was raised in Gen1 given fructose and controls, whereas glucose transporter 5 and fatty acid synthase expression were only raised with fructose. Gen1 rats weighed more than Gen0 throughout the study, although fructose feeding raised the percent body fat but not body weight. We show that long-term habituation to the living environment has a profound impact on the animal's metabolic responses to nutritional intervention and pregnancy. This has important implications for interpreting many studies investigating the influence of maternal consumption of fructose on pregnancy outcomes and offspring to date. [ABSTRACT FROM AUTHOR]

Although causality is yet to be confirmed, a considerable volume of research has explored the relationships between cow milk consumption, type II diabetes, and cardiovascular disease. Contrastingly, it has not been comprehensively examined whether milk of non-bovine origin can provide cardiometabolic protection. This narrative review outlines the marked differences in macronutrient composition, particularly protein and lipid content, and discusses how whole milk product (and individual milk ingredients) from different species could impact cardiometabolic health. There is some data, although primarily from compositional analyses, animal studies, and acute clinical trials, that non-bovine milk (notably sheep and goat milk) could be a viable substitute to cow milk for the maintenance, or enhancement, of cardiometabolic health. With a high content of medium-chain triglycerides, conjugated linoleic acid, leucine, and essential minerals, sheep milk could assist in the prevention of metabolic-related disorders. Similarly, albeit with a lower content of such functional compounds relative to sheep milk, goat and buffalo milk could be plausible counterparts to cow milk. However, the evidence required to generate nutritional recommendations for 'non-bovine milk' is currently lacking. Longer-term randomised controlled trials must assess how the bioactive ingredients of different species' milks collectively influence biomarkers of, and subsequently incidence of, cardiometabolic health. [ABSTRACT FROM AUTHOR]

Information regarding the spread and effect of coffee and caffeine intake by individuals with type II diabetes remains unclear. This study aims to identify the amount and sources of habitual caffeine intake by individuals with type II diabetes and to investigate its association with other health outcomes, especially HbA1c. This is a cross-sectional survey involving 100 people medically defined as having type II diabetes comprising both genders, recruited from a care centre. All participants completed a caffeine semi-quantitative food frequency questionnaire (C-FFQ) to estimate their caffeine consumption, a two day 24-h recall, and a detailed questionnaire. The average caffeine intake was calculated from all sources and the differences in mean by gender were tested using a regression model (adjusted to important confounders). Regression models were used to verify the association between average caffeine intake on HbA1c and other health outcomes with adjustment for important confounders. A p value < 0.05 represented statistical significance. Arabic coffee (gahwa) and tea were the most common sources of caffeine among Saudi adults living with diabetes. Average caffeine intake for the whole sample was 194 ± 165 mg/day, which is 2.3 ± 2 mg/kg. There was an inverse association between caffeine intake and age: difference in mean −3.26 mg/year (95%CI: −5.34, −1.18; p = 0.003). Males had significantly higher consumption of caffeine compared to females: difference in mean 90.7 mg/day (95%CI: 13.8, 167.6; p = 0.021). No association was found between average caffeine intake and HbA1C or any other cardiovascular risk factors. This information can help public health practitioners and policy makers when assessing the risk of caffeine consumption among this vulnerable group. [ABSTRACT FROM AUTHOR]

(E)-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants. Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool. Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases. Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders. This review describes the current knowledge on the biosynthesis and natural sources of BCP, and reviews its role and mechanisms of action in different inflammation-related metabolic and neurologic disorders. [ABSTRACT FROM AUTHOR]