EVOLUTION: Of Mice . . .

https://cyberleninka.org/article/n/1270148.pdf

The interaction of hepatic lipid and glucose metabolism in liver diseases

The prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here, we evaluated the impact of commonly consumed polyphenols, including green tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on obesity and obesity-related inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the adenosine-monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, peroxisome proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor-κB that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area and are inconsistent about the antiobesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols.

Novel insights of dietary polyphenols and obesity.

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.

Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications

https://www.journal-of-hepatology.eu/article/S0168-8278(13)00213-4/pdf

Decoding cell death signals in liver inflammation.

The liver plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually the accumulation of lipid droplets into the hepatocytes results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in beta-oxidation, very low density lipoprotein secretion, and pathways involved in the synthesis of fatty acids. In addition an increased circulating pool of non-esterified fatty acid may also to be a major determinant in the pathogenesis fatty liver disease. This review also focuses on transcription factors such as sterol-regulatory-element-binding protein-1c and peroxisome proliferator-activated receptor alpha, which promote either hepatic fatty acid synthesis or oxidation.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1439-0396.2007.00752.x

Liver lipid metabolism

As in man, canine obesity is associated with insulin resistance, dyslipidaemia and other chronic diseases. This study was designed to examine the effects of a nutritional supplement (green tea) on insulin sensitivity and plasma lipid concentrations in an obese insulin-resistant dog model. We also determined mRNA expression of two transcription factors, PPARgamma and PPARalpha, and some of their target genes, including GLUT4, lipoprotein lipase (LPL) and adiponectin. Obese dogs were divided into two groups: a green tea group (n 6); a control group (n 4). Dogs in the green tea group were given green tea extract (80 mg/kg per d) orally, just before their single daily meal, for 12 weeks. Insulin sensitivity (using a euglycaemic-hyperinsulinaemic clamp) and concentrations of plasma TAG, total cholesterol and NEFA were assessed in each group. Gene expression was measured in visceral and subcutaneous adipose tissues and in liver and skeletal muscle, by real-time PCR. At 12 weeks in the green tea group, mean insulin sensitivity index was 60 (SEM 11) % higher (P < 0.05) and TAG concentration 50 (SEM 10) % lower (P < 0.001), than baseline. PPARgamma, GLUT4, LPL and adiponectin expression were significantly higher in both adipose tissues, whilst PPARalpha and LPL expression were significantly higher in skeletal muscle, compared with baseline. These findings show that nutritional doses of green tea extract may improve insulin sensitivity and lipid profile and alter the expression of genes involved in glucose and lipid homeostasis.

/pdf/effects-of-green-tea-on-insulin-sensitivity-lipid-profile-2lboww7bun.pdf

Effects of green tea on insulin sensitivity, lipid profile and expression of PPARα and PPARγ and their target genes in obese dogs

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-γ (PPARγ) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARγ and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARγ, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARγ, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARγ expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARγ mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

/pdf/the-effects-of-obesity-associated-insulin-resistance-on-mrna-16kt9ib6dl.pdf

The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-γ target genes, in dogs

Low-consistency, high-moisture feces have been observed in large dogs (Canis lupus familiaris), compared with small dogs, and particularly in sensitive breeds (e.g., German Shepherd dogs). The aim of this work was to determine if greater colonic protein fermentation is responsible for poorer fecal quality in large sensitive dogs. Twenty-seven bitches were allotted to 4 groups based on size and digestive sensitivity: small, medium, large tolerant, and large sensitive. Five experimental diets varying in protein source [highly digestible wheat gluten (WG) vs. medium digestible poultry meal (PM), and protein concentration from 21.4 to 21.6 (LP) to 38.2 to 39.2% CP (HP)] were tested. Diets were fed for 14 d and followed by a 12-d transition period. Digestive fermentation by-products were investigated in fresh stools [ammonia, phenol, indole, and short chain fatty acids including acetate, propionate, and butyrate (C2 to C4 SCFA), branched-chain fatty acids (BCFA), and valerate] and in urine (phenol and indole). Bacterial populations in feces were identified. The PM diets resulted in greater fecal concentrations of ammonia, BCFA, valerate, indole, and C2 to C4 SCFA than WG diets (P = 0.002, P < 0.001, P = 0.039, P = 0.003, and P = 0.012, respectively). Greater concentrations of ammonia, BCFA, and valerate were found in the feces of dogs fed HP compared with LP diets (P < 0.001, P < 0.001, and P = 0.012, respectively). The concentrations of ammonia, valerate, phenol, and indole in feces of large sensitive dogs were greater (P < 0.001, P < 0.001, P = 0.002, and P = 0.019, respectively) compared with the other groups. The Enterococcus populations were greater in feces of dogs fed with PMHP rather than WGLP diets (P = 0.006). Urinary phenol and indole excretion was greater when dogs were fed PM than WG diets (P < 0.001 and P = 0.038, respectively) and HP than LP diets (P = 0.001 and P = 0.087, respectively). Large sensitive dogs were prone to excrete a greater quantity of phenol in urine (P < 0.001). A diet formulated with highly digestible protein, such as WG, led to reduced concentrations of protein-based fermentation products in feces together with improved fecal quality in dogs, especially in large sensitive ones. Poor fecal quality in large sensitive dogs could be partly related to the pattern of protein fermentation in the hindgut.

/pdf/influence-of-dietary-protein-content-and-source-on-colonic-3dr86dugsc.pdf

Influence of dietary protein content and source on colonic fermentative activity in dogs differing in body size and digestive tolerance

Dietary composition affects body composition; the role of fat and carbohydrates is well documented (1,2). Proteins are more satiating than carbohydrates, may produce different effects on glycemia (2), and are more thermogenic (1). Indeed the efficiency of cellular conversion of energy to high-energy yielding phosphate bonds from fatty acids is 90%, from carbohydrates 75%, but only 55% for amino acids (3). High-protein diets produced greater weight loss in some studies of obese humans (4,5) but not others (6). Other human studies found that although the high-protein diet did not promote weight loss in excess of control diets, it did preserve lean tissue mass (7) and promoted the loss of fat tissue (8). Companion animals also suffer from obesity (9), and a highprotein, energy-restricted diet was successful in reducing the body weight and body fat of overweight dogs (10) and cats (11), and in conserving lean body mass of dogs (12). However, there have been few studies of the effects of protein intake on the body composition in normal-weight individuals of any species. The current study aimed to determine the effect of a limited energy intake of a high-protein diet on the body composition and least observed metabolism (LOM) of adult neutered cats. MATERIALS AND METHODS

/pdf/high-protein-intake-affects-lean-body-mass-but-not-energy-3pwk6qmsis.pdf

Véronique Leray

Papers

Liver lipid metabolism

Effects of green tea on insulin sensitivity, lipid profile and expression of PPARα and PPARγ and their target genes in obese dogs

The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-γ target genes, in dogs

Influence of dietary protein content and source on colonic fermentative activity in dogs differing in body size and digestive tolerance

High Protein Intake Affects Lean Body Mass but Not Energy Expenditure in Nonobese Neutered Cats