The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11β hydroxysteroid dehydrogenase type 1 (11β HSD-1). We created transgenic mice overexpressing 11β HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11β HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome.

http://science.sciencemag.org/content/sci/294/5549/2166.full.pdf

A Transgenic Model of Visceral Obesity and the Metabolic Syndrome

The Biologically Active Isomers of Conjugated Linoleic Acid

▪ Abstract Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids found in beef, lamb, and dairy products that exist as positional and stereo-isomers of octadecadienoate (18:2). Over the past two decades numerous health benefits have been attributed to CLA in experimental animal models including actions to reduce carcinogenesis, atherosclerosis, onset of diabetes, and body fat mass. The accumulation of CLA isomers and several elongated/desaturated and β-oxidation metabolites have been found in tissues of animals fed diets with CLA. Molecular mechanisms of action appear to include modulation of eicosanoid formation as well as regulation of the expression of genes coding for enzymes known to modulate macronutrient metabolism. This review focuses on health benefits, metabolism, and potential mechanisms of action of CLA and postulates the implications regarding dietary CLA for human health.

Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action.

Growing consumer interest in grass-fed beef products has raised a number of questions with regard to the perceived differences in nutritional quality between grass-fed and grain-fed cattle. Research spanning three decades suggests that grass-based diets can significantly improve the fatty acid (FA) composition and antioxidant content of beef, albeit with variable impacts on overall palatability. Grass-based diets have been shown to enhance total conjugated linoleic acid (CLA) (C18:2) isomers, trans vaccenic acid (TVA) (C18:1 t11), a precursor to CLA, and omega-3 (n-3) FAs on a g/g fat basis. While the overall concentration of total SFAs is not different between feeding regimens, grass-finished beef tends toward a higher proportion of cholesterol neutral stearic FA (C18:0), and less cholesterol-elevating SFAs such as myristic (C14:0) and palmitic (C16:0) FAs. Several studies suggest that grass-based diets elevate precursors for Vitamin A and E, as well as cancer fighting antioxidants such as glutathione (GT) and superoxide dismutase (SOD) activity as compared to grain-fed contemporaries. Fat conscious consumers will also prefer the overall lower fat content of a grass-fed beef product. However, consumers should be aware that the differences in FA content will also give grass-fed beef a distinct grass flavor and unique cooking qualities that should be considered when making the transition from grain-fed beef. In addition, the fat from grass-finished beef may have a yellowish appearance from the elevated carotenoid content (precursor to Vitamin A). It is also noted that grain-fed beef consumers may achieve similar intakes of both n-3 and CLA through the consumption of higher fat grain-fed portions.

/pdf/a-review-of-fatty-acid-profiles-and-antioxidant-content-in-56v8grm3id.pdf

A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef, lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9, trans-11 (c9t11) isomer. Commercially available CLA is usually a 1:1 mixture of c9t11 and trans-10, cis-12 (t10c12) isomers with other isomers as minor components. Conjugated LA isomer mixture and c9t11 and t10c12 isomers alone have been attributed to provide several health benefits that are largely based on animal and in vitro studies. Conjugated LA has been attributed many beneficial effects in prevention of atherosclerosis, different types of cancer, hypertension and also known to improve immune function. More recent literature with availability of purified c9t11 and t10c12 isomers suggests that t10c12 is the sole isomer involved in antiadipogenic role of CLA. Other studies in animals and cell lines suggest that the two isomers may act similarly or antagonistically to alter cellular function and metabolism, and may also act through different signaling pathways. The effect of CLA and individual isomers shows considerable variation between different strains (BALB/C mice vs. C57BL/6 mice) and species (e.g., rats vs. mice). The dramatic effects seen in animal studies have not been reflected in some clinical studies. This review comprehensively discusses the recent studies on the effects of CLA and individual isomers on body composition, cardiovascular disease, bone health, insulin resistance, mediators of inflammatory response and different types of cancer, obtained from both in vitro and animal studies. This review also discusses the latest available information from clinical studies in these areas of research.

Biological effects of conjugated linoleic acids in health and disease.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.

https://diabetes.diabetesjournals.org/content/diabetes/49/9/1534.full.pdf

Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.

PROBLEM TO BE SOLVED: To obtain a body fat reducing agent having high stability with slight adverse effects by including a dioxabicyclooctane derivative as an active ingredient SOLUTION: This body fat reducing agent is obtained by including a dioxabicyclo[330]octance derivative represented by the formula (R1 to R6 are each H or a 1-3C alkyl or R1 and R2 and/or R4 and R5 together denote methylene or ethylene; n, m and 1 are each 0 or 1), eg sasemin, sesaminol, episesamin, episesaminol, sesamolin, 2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4- hydroxyphenyl)-3,7-dioxabicyclo[330]octane or 2,6-bis-(3-methoxy-4- hydroxyphenyl)-3,7-dioxabicyclo[330]octane and a mixture thereof as an active ingredient The daily dose of the agent for an adult is preferably 1 mg to 10 g expressed in terms of the total amount of the derivative in the case of oral administration

Body fat-reducing agent comprising dioxabicyclo[3.3.0] octane derivative as active ingredient

There is provided an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient.

Method for increasing brown fat, comprising administering conjugated linoleic acid as active ingredient

Agent for increasing brown fat, comprising conjugated linoleic acid as active ingredient

PROBLEM TO BE SOLVED: To obtain the subject slightly sticky powder making it possible to efficiently take the conjugated linolic acid and useful for drinks, foods, etc., by mixing a prescribed amount of a specific oily liquid with a prescribed amount of gum arabic and a prescribed amount of water to prepare an O/W type emulsion and subsequently drying and pulverizing the emulsion. SOLUTION: This conjugated linolic acid powder is obtained by mixing 60-85 pts.wt. of an oily liquid containing >=65 wt.% of the conjugated linolic acid with 15-40 pts.wt. of gum arabic and a proper amount of water to prepare an O/W type emulsion, and subsequently drying and pulverizing the emulsion. It is preferable to add an antioxidant containing vitamin E as a main component to the conjugated linolic acid powder.

Hitoshi Okuyama

Papers

Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.

Body fat-reducing agent comprising dioxabicyclo[3.3.0] octane derivative as active ingredient

Method for increasing brown fat, comprising administering conjugated linoleic acid as active ingredient

Agent for increasing brown fat, comprising conjugated linoleic acid as active ingredient

Conjugated linolic acid powder and its production