1 00:00:05,600 --> 00:00:09,479 Speaker 1: Hey, everyone, welcome to another edition of Wisdom Wednesdays. Now, 2 00:00:09,600 --> 00:00:13,119 Speaker 1: for decades, we've been told that the key to controlling 3 00:00:13,160 --> 00:00:17,280 Speaker 1: blood pressure is simple, eat less salt or sodium. And 4 00:00:17,320 --> 00:00:21,119 Speaker 1: in fact, the us Diartry guidelines still recommend limiting sodium 5 00:00:21,200 --> 00:00:24,079 Speaker 1: intake to about two point three grams per day, and 6 00:00:24,160 --> 00:00:27,400 Speaker 1: here in Australia it's two grams per day. But when 7 00:00:27,480 --> 00:00:30,560 Speaker 1: you dig into the science, the story is actually a 8 00:00:30,600 --> 00:00:34,360 Speaker 1: lot more complicated. Some long term studies have actually found 9 00:00:34,360 --> 00:00:39,400 Speaker 1: something quite surprising that lower sodium intake can sometimes associate 10 00:00:39,479 --> 00:00:43,400 Speaker 1: with higher blood pressure. And there's another curious observation is 11 00:00:43,440 --> 00:00:46,000 Speaker 1: that people with obesity tend to be. 12 00:00:46,560 --> 00:00:49,560 Speaker 2: Far more salt sensitive than lean individuals. 13 00:00:49,760 --> 00:00:52,040 Speaker 1: So the big question is why Today we're going to 14 00:00:52,040 --> 00:00:55,320 Speaker 1: explore that and through a fascinating piece of research that 15 00:00:55,600 --> 00:00:59,320 Speaker 1: may provide a completely new way of thinking about high 16 00:00:59,320 --> 00:01:05,120 Speaker 1: blood pressure. And it really involves a complex interaction between 17 00:01:05,160 --> 00:01:08,920 Speaker 1: body fat, the brain, and the nervous system. So most 18 00:01:08,920 --> 00:01:12,479 Speaker 1: people think about body fat really think of it as 19 00:01:12,560 --> 00:01:19,000 Speaker 1: a passive energy storage, but biologically speaking, fat is actually 20 00:01:19,120 --> 00:01:22,080 Speaker 1: an endocrine organ and I've talked about this before. That 21 00:01:22,240 --> 00:01:26,600 Speaker 1: means that it releases its own hormones that communicate with 22 00:01:26,800 --> 00:01:29,399 Speaker 1: other parts of the body, and one of the most 23 00:01:29,440 --> 00:01:33,560 Speaker 1: important of these hormones is something called leptin. Now, leptin's 24 00:01:33,640 --> 00:01:37,880 Speaker 1: classic role is to signal the brain how much energy 25 00:01:37,920 --> 00:01:43,480 Speaker 1: we've actually stored, and when fat mass increases, leptin levels rise. 26 00:01:43,880 --> 00:01:46,959 Speaker 1: And what leptin does is two things. Two main things. 27 00:01:47,400 --> 00:01:50,320 Speaker 1: One is that it's about cessation of eating. It tells 28 00:01:50,360 --> 00:01:53,800 Speaker 1: you you've had enough eating. And it actually drives voluntary 29 00:01:53,840 --> 00:01:57,600 Speaker 1: physical activity. And when they block the leptin gene in 30 00:01:57,840 --> 00:02:02,520 Speaker 1: healthy mice and rats, they stop moving and they over eight. 31 00:02:02,960 --> 00:02:06,320 Speaker 2: Right. And this is why you don't see a. 32 00:02:06,360 --> 00:02:11,160 Speaker 1: Fat rattlesnake or a fat line, because leptin is actually 33 00:02:11,240 --> 00:02:14,840 Speaker 1: a very powerful controller of body weight. But because we 34 00:02:14,919 --> 00:02:17,640 Speaker 1: have appetite and we have all these ultra processed foods 35 00:02:17,639 --> 00:02:24,160 Speaker 1: and center frey lifestyles, our leptin control system can become dysfunctional. 36 00:02:24,240 --> 00:02:30,600 Speaker 1: And that is a state where we continue to accumulate 37 00:02:30,680 --> 00:02:33,840 Speaker 1: leptin as we're accumulating body fat, and that is known 38 00:02:33,880 --> 00:02:38,040 Speaker 1: as hyper leptinemia. Right, So very high levels of leptin, 39 00:02:38,360 --> 00:02:41,799 Speaker 1: and there's actually research showing that you can get leptin resistance. 40 00:02:41,919 --> 00:02:46,200 Speaker 1: The higher the leptin, the less effective it comes. And 41 00:02:46,320 --> 00:02:51,240 Speaker 1: as I said, Other studies show consistently that higher leptin 42 00:02:51,360 --> 00:02:54,680 Speaker 1: levels then also correlate with high blood pressure. 43 00:02:55,120 --> 00:02:57,640 Speaker 2: So is it correlation or is it causation. 44 00:02:58,320 --> 00:03:01,440 Speaker 1: Now, one pretty cool study that I just read published 45 00:03:01,440 --> 00:03:05,920 Speaker 1: in Cell Metabolism, really answers this question, and they examined 46 00:03:05,960 --> 00:03:10,360 Speaker 1: whether leptin itself might trigger changes in the brain that 47 00:03:10,560 --> 00:03:12,360 Speaker 1: eventually lead to hypertension. 48 00:03:12,760 --> 00:03:14,040 Speaker 2: So let's talk about this study. 49 00:03:14,040 --> 00:03:17,519 Speaker 1: It was published in Cell Metabolism, and the researchers fed 50 00:03:17,680 --> 00:03:21,639 Speaker 1: mice a high sugar, high fat diet that was designed 51 00:03:21,680 --> 00:03:24,960 Speaker 1: to induce obesity, and what they find is that the 52 00:03:24,960 --> 00:03:30,000 Speaker 1: blood pressure didn't increase immediately. Something else happened. First, as 53 00:03:30,000 --> 00:03:34,560 Speaker 1: the mice gained with it, the researchers noticed structural changes 54 00:03:34,600 --> 00:03:39,600 Speaker 1: occurring in the brain and specifically in the hypothalmis. Now 55 00:03:39,640 --> 00:03:42,840 Speaker 1: you may well know that the hypothalmis is essentially the 56 00:03:42,880 --> 00:03:47,880 Speaker 1: body's physiological control center or command center. We know that 57 00:03:47,960 --> 00:03:53,280 Speaker 1: hypothalmis regulates hunger and satiety, It regulates hormones, it regulates temperature, 58 00:03:53,600 --> 00:03:58,560 Speaker 1: it regulates fluid balance, it regulates the stress response, and importantly, 59 00:03:58,880 --> 00:04:03,280 Speaker 1: it regulates blood pressure. Now, the hypothalmis does this partly 60 00:04:03,800 --> 00:04:08,880 Speaker 1: by controlling your sympathetic nervous system the classic fighter flight response, 61 00:04:09,400 --> 00:04:13,560 Speaker 1: and when the sympathetic nervous system is activated chronically, it 62 00:04:13,600 --> 00:04:18,800 Speaker 1: can reise blood pressure by increasing heart rate, constricting blood vessels, 63 00:04:19,080 --> 00:04:23,080 Speaker 1: and altering kidney function and fluid retention. So what these 64 00:04:23,120 --> 00:04:27,359 Speaker 1: researchers wanted to know was could obesity some high be 65 00:04:27,560 --> 00:04:31,799 Speaker 1: altering the structure of this hypothomas of the control center, 66 00:04:32,320 --> 00:04:33,600 Speaker 1: And remarkably, that. 67 00:04:33,640 --> 00:04:35,600 Speaker 2: Is exactly what they find. 68 00:04:35,880 --> 00:04:40,080 Speaker 1: Before the mass developed high blood pressure, the researchers observe 69 00:04:40,440 --> 00:04:45,440 Speaker 1: major remodeling of blood vessels around the hypothalmus first, and 70 00:04:45,520 --> 00:04:50,040 Speaker 1: these changes included an increase in a number of blood vessels, 71 00:04:50,400 --> 00:04:55,440 Speaker 1: also a thickening of the vessel basement membranes and increased 72 00:04:55,520 --> 00:04:57,040 Speaker 1: vascular permeability. 73 00:04:57,440 --> 00:04:58,360 Speaker 2: Now what all that. 74 00:04:58,320 --> 00:05:02,720 Speaker 1: Means is that the micro architecture of the hypothalmus was 75 00:05:02,920 --> 00:05:08,240 Speaker 1: literally being rewired by an increase in body fat. And crucially, 76 00:05:09,120 --> 00:05:13,520 Speaker 1: these changes occurred before the rise in blood pressure was noticed, 77 00:05:13,560 --> 00:05:18,359 Speaker 1: so was cause causative not correlation. And even more interesting 78 00:05:18,800 --> 00:05:23,119 Speaker 1: was that the vascular remodeling occurred at exactly the same 79 00:05:23,200 --> 00:05:26,640 Speaker 1: time that leptin levels in the blood street began to 80 00:05:26,839 --> 00:05:32,360 Speaker 1: increase as the animals became obese. So the researchers really suspected, 81 00:05:33,000 --> 00:05:35,839 Speaker 1: as you would imagine, that leptin might well be the 82 00:05:35,880 --> 00:05:39,880 Speaker 1: actual trigger. So let's break down the mechanism a little bit. 83 00:05:40,000 --> 00:05:44,120 Speaker 1: So the first step begins with expanding the fat tissue. 84 00:05:44,240 --> 00:05:48,240 Speaker 1: As your fat mass increases, fat sales increase the amount 85 00:05:48,320 --> 00:05:52,160 Speaker 1: of leptin that they release into the bloodstream. Step two 86 00:05:52,240 --> 00:05:56,440 Speaker 1: then occurs in the brain. Leptin crosses into the hypothalmis 87 00:05:56,839 --> 00:06:02,160 Speaker 1: and interacts with astrocytes. These are victualized support cells that 88 00:06:02,320 --> 00:06:07,640 Speaker 1: help regulate the blood brain barrier and the local micro. 89 00:06:07,480 --> 00:06:09,599 Speaker 2: Environment around your neurons. 90 00:06:09,720 --> 00:06:14,840 Speaker 1: And these astrocytes actually respond to leptin by activating a 91 00:06:14,880 --> 00:06:21,680 Speaker 1: molecular signaling pathway. It involves hifon and VGF. Now VEGF 92 00:06:21,760 --> 00:06:23,680 Speaker 1: you may have heard me talk about this before. This 93 00:06:23,720 --> 00:06:28,560 Speaker 1: stands for vascular endothelial growth factor, and as the name suggests, 94 00:06:29,000 --> 00:06:31,880 Speaker 1: it stimulates the formation of new blood vessels. 95 00:06:32,560 --> 00:06:35,800 Speaker 2: And in step three was angiogenesis. 96 00:06:35,839 --> 00:06:39,919 Speaker 1: This is the growth of new microvessels within the hypothalmus, 97 00:06:40,279 --> 00:06:46,160 Speaker 1: and this remodeling changes what sciencests call the gliovascular interface, 98 00:06:46,480 --> 00:06:50,520 Speaker 1: which is the structural relationship between the brain cells and 99 00:06:50,560 --> 00:06:54,000 Speaker 1: the blood vessels. Step four is where and it gets 100 00:06:54,080 --> 00:06:56,360 Speaker 1: really gikky here. But this is where the physiology becomes 101 00:06:56,480 --> 00:07:02,080 Speaker 1: really interesting. The altered vascular in environment changes how the 102 00:07:02,279 --> 00:07:07,440 Speaker 1: neurons in the hypothalmis process signals that regulate the sympathetic 103 00:07:07,520 --> 00:07:11,800 Speaker 1: nervous system, and the result is a persistent increase in. 104 00:07:11,840 --> 00:07:13,720 Speaker 2: Sympathetic nerve activity. 105 00:07:14,200 --> 00:07:17,880 Speaker 1: And chronic activation of the sympathetic nervous system is one 106 00:07:17,880 --> 00:07:20,200 Speaker 1: of the classic drivers of hypertension. 107 00:07:20,560 --> 00:07:21,520 Speaker 2: And not only does. 108 00:07:21,400 --> 00:07:25,560 Speaker 1: It do that, but it really has widespread effects throughout 109 00:07:25,560 --> 00:07:28,880 Speaker 1: your body. You do not want to be in chronic 110 00:07:28,960 --> 00:07:32,880 Speaker 1: activation of your sympathetic nervous system. That is basically being 111 00:07:32,920 --> 00:07:38,120 Speaker 1: in a stressed state. So obesity actually causes a stress 112 00:07:38,160 --> 00:07:38,760 Speaker 1: on the body. 113 00:07:38,840 --> 00:07:39,720 Speaker 2: And here's how it works. 114 00:07:39,760 --> 00:07:46,120 Speaker 1: Basically, obesity causes higher leptin, which causes hypothalmic vascular remodeling, 115 00:07:46,320 --> 00:07:51,120 Speaker 1: which causes sympathetic overactivity, which then causes the increased blood pressure. 116 00:07:51,920 --> 00:07:56,760 Speaker 1: So the big question here is the damage permanent. And 117 00:07:56,800 --> 00:07:59,520 Speaker 1: this is where it gets encouraging because the researchers wanted 118 00:07:59,560 --> 00:08:02,800 Speaker 1: to know that, so they performed a follow up experiment 119 00:08:03,120 --> 00:08:05,840 Speaker 1: and they took these obese mice and they switched them 120 00:08:05,840 --> 00:08:08,840 Speaker 1: back to a normal diet, which caused the animals to 121 00:08:08,920 --> 00:08:12,080 Speaker 1: lose weight and lower their leptin levels, and when they 122 00:08:12,080 --> 00:08:16,200 Speaker 1: did that, they saw that the abnormal blood pressure growth 123 00:08:16,240 --> 00:08:21,240 Speaker 1: in the hypothalm was actually reversed, so the microvascular structure 124 00:08:21,600 --> 00:08:26,000 Speaker 1: returned almost completely to what was seen in lean animals. 125 00:08:26,320 --> 00:08:29,320 Speaker 1: In other words, these brilling changes weren't permanent, at least 126 00:08:29,320 --> 00:08:33,040 Speaker 1: in the mouse model. Now we don't know if they 127 00:08:33,080 --> 00:08:35,440 Speaker 1: were obese, if they'd been left to be obese for 128 00:08:35,520 --> 00:08:39,480 Speaker 1: months and months and months, whether that remodeling would actually 129 00:08:39,520 --> 00:08:43,000 Speaker 1: have happening. But what it does suggest is that obesely 130 00:08:43,480 --> 00:08:47,800 Speaker 1: might leave what some scientists referred to as a metabolic scar, 131 00:08:48,320 --> 00:08:53,040 Speaker 1: but that scar may still be modifiable if the underlying 132 00:08:53,559 --> 00:08:58,199 Speaker 1: environment actually improves. So for me, this research provides an 133 00:08:58,240 --> 00:09:03,280 Speaker 1: intriguing explanation for something that doctors have observed for years 134 00:09:03,480 --> 00:09:08,400 Speaker 1: is that people with obesity often exhibit salt sensitive hypertension, 135 00:09:08,720 --> 00:09:12,360 Speaker 1: and that means that blood pressure rises much more dramatically 136 00:09:12,840 --> 00:09:16,280 Speaker 1: in response to sodium intake than it doesn't lean individuals. 137 00:09:17,400 --> 00:09:20,640 Speaker 1: And one possibility here, a very clear one, is the 138 00:09:20,760 --> 00:09:25,600 Speaker 1: hypotholic remodeling that we've just discussed actually alters the neural 139 00:09:25,640 --> 00:09:31,000 Speaker 1: circuits that regulate kidney sodium handling. So remember, the sympathetic 140 00:09:31,040 --> 00:09:35,679 Speaker 1: nervous system directly affects the kidneys, and if sympathetic activity increases, 141 00:09:35,720 --> 00:09:38,640 Speaker 1: the kidneys tend to retain more sodium and water, which 142 00:09:38,720 --> 00:09:40,880 Speaker 1: raises blood pressure. And by the way, this is why 143 00:09:40,960 --> 00:09:44,920 Speaker 1: chronic stress can also reaise blood pressure, because it's the 144 00:09:45,000 --> 00:09:49,240 Speaker 1: sympathetic nervous system then influencing the kidneys to retain more 145 00:09:49,280 --> 00:09:50,120 Speaker 1: sodium and water. 146 00:09:50,360 --> 00:09:53,560 Speaker 2: So I think this research really does converge. 147 00:09:53,960 --> 00:09:58,280 Speaker 1: So really, obesity may prime the brain in a way 148 00:09:58,400 --> 00:10:02,480 Speaker 1: that makes the body much more reactive to sodium intake. 149 00:10:02,840 --> 00:10:04,959 Speaker 1: In other words, the problem is not just salt alone, 150 00:10:05,320 --> 00:10:09,040 Speaker 1: but how the brain interprets salt signals when influenced by 151 00:10:09,080 --> 00:10:10,000 Speaker 1: excess body fat. 152 00:10:10,400 --> 00:10:11,360 Speaker 2: So what does it all mean. 153 00:10:11,679 --> 00:10:16,920 Speaker 1: It means that hypertension, particularly in obesity, is not simply 154 00:10:17,280 --> 00:10:22,200 Speaker 1: about a dietary sodium problem. It involves these complex neuroendocrime 155 00:10:22,320 --> 00:10:26,360 Speaker 1: pathways that link fat tissue, the brain, vascular system, and 156 00:10:26,400 --> 00:10:29,000 Speaker 1: the nervous system. Now, all of this doesn't mean that 157 00:10:29,080 --> 00:10:32,720 Speaker 1: sodium intake is irrelevant. But if you're metabolically healthy and 158 00:10:32,800 --> 00:10:36,200 Speaker 1: if you're lean, do you really need to manage your 159 00:10:36,240 --> 00:10:40,000 Speaker 1: salt intake or is it just people who are overweight 160 00:10:40,160 --> 00:10:43,760 Speaker 1: who need to manage the salt intake. And this really 161 00:10:43,920 --> 00:10:47,679 Speaker 1: ties in with research that shows that the single best 162 00:10:47,720 --> 00:10:50,760 Speaker 1: way to lower your blood pressure if you're overweight is 163 00:10:50,800 --> 00:10:56,000 Speaker 1: to actually lose weight. And now we understand the mechanisms. So, 164 00:10:56,360 --> 00:10:59,760 Speaker 1: if you're lean, do you really need to follow the 165 00:10:59,800 --> 00:11:02,640 Speaker 1: Diar Tree guidelines around salting tick? I certainly don't, but 166 00:11:02,800 --> 00:11:05,040 Speaker 1: you can make your own call. But if your obease 167 00:11:05,280 --> 00:11:10,199 Speaker 1: or overweight, then managing your weight would be the first step. 168 00:11:10,880 --> 00:11:14,440 Speaker 1: But understand that if you are overweight, you are much 169 00:11:14,480 --> 00:11:18,920 Speaker 1: more likely to be much more salt sensitive than lean individuals. So, 170 00:11:19,600 --> 00:11:23,120 Speaker 1: like everything in the dietary guidelines, and there is no 171 00:11:23,200 --> 00:11:27,040 Speaker 1: one size fits all, we read a much more nuanced approach. 172 00:11:27,640 --> 00:11:30,240 Speaker 2: So that's it for this week, folks, Catch you next time.