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Methods For Inducing Adipocyte Browning, Improving Metabolic Flexibility, And Reducing Detrimental White Adipose Tissue Deposition And Dysfunction

a metabolic flexibility and browning technology, applied in the field of inducing adipocyte browning, improving metabolic flexibility, and reducing detrimental white adipose tissue deposition and dysfunction, can solve problems such as adversely affecting metabolic health, and achieve the effects of improving metabolic flexibility, metabolic flexibility, and improving metabolic flexibility

Inactive Publication Date: 2019-11-28
MEAD JOHNSON NUTRITION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In another aspect, the disclosure relates to a method for improving metabolic flexibility in a subject. The method can include administering to the subject a nutritional composition comprising extensively hydrolyzed casein, extensively hydrolyzed casein fractions, or combinations thereof, and / or a long chain polyunsaturated fatty acid. In certain embodiments, administration of the nutritional composition to the subject when the subject is an infant improves the metabolic flexibility of the subject in adolescence and / or adulthood, and wherein metabolic flexibility is measured by (a) reduced plasma levels of at least one of total cholesterol, total triglycerides, free fatty acids, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the subject in response to a high fat diet, as compared to a subject who has not received the nutritional composition; or (b) decreased fasting insulin levels, improved glucose tolerance, enhanced insulin sensitivity; and / or increased plasma adiponectin levels, as compared to a subject who has not received the nutritional composition.

Problems solved by technology

Accumulation of excess white adipose tissue (WAT) adversely affects metabolic health.

Method used

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  • Methods For Inducing Adipocyte Browning, Improving Metabolic Flexibility, And Reducing Detrimental White Adipose Tissue Deposition And Dysfunction
  • Methods For Inducing Adipocyte Browning, Improving Metabolic Flexibility, And Reducing Detrimental White Adipose Tissue Deposition And Dysfunction
  • Methods For Inducing Adipocyte Browning, Improving Metabolic Flexibility, And Reducing Detrimental White Adipose Tissue Deposition And Dysfunction

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0238]The following example demonstrates that eHC, ARA / DHA and their combination is capable of inducing adipocyte browning and reducing metabolic disturbances later in life. eHC is denoted as “casein” in the figures.

Ucp-1 Luciferase Knock-in Mouse Model

[0239]UCP1 is a key molecule in browning, and increased expression is a measure for browning induction. In Ucp-1 luciferase knock-in reporter mice, in vivo imaging of luciferase activity directly reflects the UCP1 protein level in vivo. In this study, mice were fed normal chow, and supplementation with ARA / DHA, eHC and their combination began post-weaning at 4 weeks of age and continued for 8 weeks. At 12 weeks of age, animals were switched to a high fat diet (HFD, including test ingredients ARA / DHA and / or eHC), and feeding was continued for another 12 weeks. Browning activity (as illustrated by luciferase signal) at different adipose tissue depots and browning relevant marker genes were analyzed at different time points. Other parame...

example 2

[0253]Table 3 provides an exemplary embodiment of a nutritional composition according to the present disclosure and describes the amount of each ingredient to be included per 100 Kcal serving.

TABLE 3Nutrition profile of an example nutritional compositionper 100 KcalNutrientMinimumMaximumeHC (g)1.07.0Carbohydrates (g)622Fat (g)1.37.2Prebiotic (g)0.31.2DHA (g)422Beta glucan (mg)2.917Probiotics (cfu)0.55.0Vitamin A (IU)9.60 × 1053.80 × 108Vitamin D (IU)134921Vitamin E (IU)22126Vitamin K (mcg)0.85.4Thiamin (mcg)2.918Riboflavin (mcg)63328Vitamin B6 (mcg)68420Vitamin B12 (mcg)52397Niacin (mcg)0.20.9Folic acid (mcg)6905881Panthothenic acid (mcg)866Biotin (mcg)2321211Vitamin C (mg)1.45.5Choline (mg)4.924Calcium (mg)4.943Phosphorus (mg)68297Magnesium (mg)54210Sodium (mg)4.934Potassium (mg)2488Chloride (mg)82346Iodine (mcg)53237Iron (mg)8.979Zinc (mg)0.72.8Manganese (mcg)0.72.4Copper (mcg)7.241

[0254]Although preferred embodiments of the disclosure have been described using specific terms, dev...

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Abstract

This disclosure relates to methods of inducing adipocyte browning, supporting metabolic flexibility, and / or reducing detrimental WAT deposition or reducing WAT dysfunction in a subject by administering extensively hydrolyzed casein and / or fractions N thereof (“eHC”) to the subject, and / or by administering a long chain polyunsaturated fatty acid (e.g., docosahexaenoic acid and / or arachidonic acid) to the subject.

Description

TECHNICAL FIELD[0001]This disclosure relates to methods of inducing adipocyte browning, supporting metabolic flexibility, and / or reducing detrimental white adipose tissue (WAT) deposition or reducing WAT dysfunction by administering extensively hydrolyzed casein and / or fractions thereof (“eHC”) to a subject, and / or by administering a long chain polyunsaturated fatty acid (e.g., docosahexaenoic acid and / or arachidonic acid).BACKGROUND[0002]Accumulation of excess white adipose tissue (WAT) adversely affects metabolic health. In contrast, brown adipose tissue (BAT) confers benefits on metabolic health, and is characterized by increased energy-expenditure capacity in the form of heat (thermogenesis). The negative effects of WAT may be reduced by inducing the development of brown adipocytes or beige adipocytes (also called ‘brite’ (brown-in-white), induced BAT, recruitable BAT and wBAT (white adipose BAT) in WAT, a process called “browning.” (See, Harms et al. (2013) NATURE MEDICINE 19:1...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A23L33/19A23L33/12A61K38/01A23L33/125A23L33/18A61K35/741A61K31/716
CPCA23L33/19A23L33/12A61K45/06A23L33/18A23L33/125A61K38/018A61K35/741A61K31/716A23V2002/00A61K31/202H01L2224/48472H01L2224/48137H01L2224/73265H01L2224/48091H01L2224/48227H01L2224/32225H01L2224/92247A61K2300/00A23V2200/3262A23V2200/328A23V2250/1862A23V2250/1868A23V2250/28A23V2250/54246A23V2250/55H01L2924/00014H01L2924/00A61K31/702H01L23/49568H01L23/49513
Inventor ZHONG, YANSCHOEMAKER, MARIEKE HENRIETTELAMBERS, TEARTSE TIMVAN TOL, ERIC ALEXANDER FRANCISCUS
Owner MEAD JOHNSON NUTRITION
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