Slide 1: Insulin Resistance: Friend or Foe?
6/1/20 Insulin Resistance: Friend or Foe? Ric R. Grummer Emeritus Professor Department of Dairy Science University of Wisconsin-Madison 1 Metabolic Regulation of Body Fat Mobilization • Regulation is very complex • There are many hormones involved • One of the most important hormones is insulin 2 1
Slide 2: Metabolic Roles of Insulin
6/1/20 Metabolic Roles of Insulin • Facilitates glucose entry into cells • Inhibits hepatic gluconeogenesis • Inhibits hepatic glycogenolysis • Enhances adipose fatty acid synthesis • Enhances adipose triglyceride synthesis • Enhances adipose uptake of TG • Inhibits adipose lipolysis 3 Insulin resis
Slide 3: Insulin Resistance (IR) in Transition Cows
6/1/20 Insulin Resistance (IR) Definition: “Normal concentrations of insulin produce a less than normal biologic response.” (Kahn, 1978) 5 IR in Transition Cows • IR is observed in mammals during late gestation and early lactation: Why? – IR in muscle decreases glucose uptake – IR in adipose decreas
Slide 4: IR: Important Concepts; Extreme Examples: Grizzly Bears
6/1/20 IR: Important Concepts • It is not all on or all off • Cows “purposely” undergo insulin resistance to support gestation and lactation • An example of homeorhesis: the orchestrated or coordinated control in metabolism of body tissues to support a physiological state • It is a normal biological
Slide 5: Extreme Examples: Hooded Fur Seal; Transition Cow Plasma NEFA
6/1/20 Extreme Examples: Hooded Fur Seal • Lactation period of less than 4 days – Cow does not eat – Pups gain 7 kg BW/d, most of which is blubber (fat) deposition – Direct transfer of maternal (blubber) to milk (61% Fat) to pup (blubber) 9 Transition Cow Plasma NEFA 1000 800 NEFA, uM 600 400 200 -2
Slide 6: IR: A Friend or Foe??
6/1/20 NEFA uptake by liver during the transition period. (Reynolds et al., 2003) 13x increase *Estimate 11 IR: A Friend or Foe?? • Can cows become too insulin resistant? – Too much fatty acid mobilization? Conversely: – Too much glucose and fatty acid available to the mammary gland to support lacta
Slide 7: Does too much IR = too much NEFA?
6/1/20 Does too much IR = too much NEFA = ????????? 13 Top 10 Reasons to Hate Elevated Blood NEFA 1. Increases liver fat (Bobe et al., 2004) 2. Increases hepatic ketone production (Cadorniga et a., 1997) 3. Increased risk of DA (Ospina et al., 2010) 4. Decreases hepatic gluconeogenesis (Li et al., 2
Slide 8: Two Reasons to Love Elevated Blood NEFA
6/1/20 Two Reasons to Love Elevated Blood NEFA • Provide energy for tissues including the mammary gland • Provide precursors for milk fat synthesis 15 16 8
Slide 9: Controlled Energy "Goldilocks" Diet
6/1/20 Controlled Energy “Goldilocks” Diet • High in low quality forage, typically straw • When consumed ad libitum, energy requirements are met but not exceeded • Cows are less insulin resistant – Lower rates of lipolysis – Less fatty liver – Lower BHBA 17 Response to Feeding Controlled Energy Diet
Slide 10: Response to Feeding Controlled Energy Diets
6/1/20 Response to Feeding Controlled Energy Diets BHBA, Percentage Change 19 Response to Feeding Controlled Energy Diets Liver TG, Percentage Change 20 10
Slide 11: What is rarely talked about…
6/1/20 What is rarely talked about…..... 21 Response to Feeding Controlled Energy Diets -8.92 22 11
Slide 12: Response to Feeding Controlled Energy Diets
6/1/20 Response to Feeding Controlled Energy Diets 23 Response to Feeding Controlled Energy Diets 24 12
Slide 13: This Data Makes Total Sense!!!!
6/1/20 This Data Makes Total Sense!!!! • Cows fed controlled energy diets mobilize less fat (NEFA) • NEFA are used by the mammary gland – Energy source – Precursor for milk fat synthesis • If you reduce NEFA availability to the mammary gland, it should not be surprising that there may be downstream
Slide 14: IR and Genetic Potential: Glucose Challenge
6/1/20 27 IR and Genetic Potential: Glucose Challenge New Zealand HF North American HF P value Milk yield, lb/d 67.8 74.7 <0.05 Fractional Turnover rate, %/min 2.0 1.8 <0.05 Glucose ½ life, min 35.0 39.5 0.08 Greater IR Chagas et al., 2009 28 14
Slide 15: What Does this Mean in the Context of NEFA and BHBA Testing?
6/1/20 What Does this Mean in the Context of NEFA and BHBA Testing? NEFA Rumen Body Fat Liver BHBA 29 Blood NEFA and BHBA • These are used as indicators of negative energy balance • Numerous studies suggest if levels get too high, milk yield is reduced and health and reproduction suffer – Postpartum
Slide 16: Dutch Study - 23 herds
6/1/20 UW- Madison study: 570 Total cows 19.7% were hyperketonemic (BHBA > 1.2 mmol/L) Note: Cow sampled twice weekly between d5 and 18 PP. HYK cows were treated with 300 ml PG/d for 3 d “may suggest that higher- producing cows became hyperketonemic due to the high energy demand for milk production
Slide 17: Hmmmmm? Bottom Line
6/1/20 “Too many of my cows are testing high for BHBA! But my cows are milking like crazy!” Hmmmmm????????? 33 Bottom Line: I am NOT against BHBA testing! Caution: Like most blood tests, interpretation of results can be complicated. One size fits all cutoffs for NEFA and BHBA may be deceptive!? If N
Slide 18: Hmmmmmmmm… Newbold quote; Historically
6/1/20 Hmmmmmmmm……… “Nutritional restriction to adipose tissue mobilisation might be necessary, but there is a philosophical problem. We have selected cows that have increased reliance on mobilised body reserves as a source of nutrients for milk production. The farmer has paid the geneticist for thi
Slide 19: Questions For You to Think About
6/1/20 Newbold’s Vision NEFA Rumen Body Fat Liver FAT BHBA Milk Choline 37 Questions For You to Think About • Are elevated [NEFA] or [BHBA] always bad??? • Do one size fit all “cut-offs” for [NEFA] or [BHBA] alarms always serve us well? Low vs high genetic potential cows? • What do you tell a dairy